Nallasivam Palanisamy: cancer researcher
Nallasivam Palanisamy is an accomplished cancer researcher specializing in prostate cancer, cancer genomics, and molecular pathology. He currently serves as an Associate Scientist in the Department of Urology at Henry Ford Health and an Adjunct Associate Professor at Michigan State University. Key contributions• Discovery of RAF gene fusions and pseudogene-associated gene fusions in prostate cancer using next-generation sequencing.• Pioneering work in developing novel biomarkers for diagnosing and treating prostate cancer.• Successfully applying next-generation sequencing for transcriptome sequencing to discover new recurrent gene fusions in various cancers.• Identifying novel approaches in FISH probe development for diagnosing recurrent chromosome translocations in cancer. Professional backgroundNallasivam Palanisamy has held positions such as Research Assistant Professor at the Michigan Center for Translational Pathology, Group Leader of Cancer Biology at the Genome Institute of Singapore, Adjunct Assistant Professor at Nanyang Technological University, and Founding Director of Research and Development at Cancer Genetics Inc. EducationPalanisamy earned B.Sc., M.Sc., M.Phil., and Ph.D. degrees in Genetics from the University of Madras and completed postdoctoral research at the University of Michigan and the University of Vermont. Recognition and achievementsHis work includes authoring over 150 peer-reviewed publications and holding five patents. He has also received significant research funding and has been an invited speaker at various events. Colleagues have praised his expertise in cancer research. Career accomplishmentsNallasivam Palanisamy: Career accomplishments in cancer researchDr. Nallasivam Palanisamy is a distinguished Associate Scientist in Urology at Henry Ford Health and an Adjunct Associate Professor at the University of Michigan, specializing in the molecular underpinnings of cancer, particularly prostate cancer. His career achievements include:• Discovery of RAF gene fusions: Palanisamy discovered recurrent RAF gene fusions in prostate cancer cases that were negative for the typical ETS gene rearrangements. He also identified these rearrangements in some cases of melanoma and gastric cancers. This discovery is crucial because RAF gene fusions are "druggable," meaning they can be targeted with existing medications like BRAF and MEK inhibitors, opening doors for targeted therapies in specific cancer subsets.• Identification of Pseudogene-Associated Gene Fusions: He also made a significant breakthrough by identifying a novel type of gene fusion involving a pseudogene, specifically a recurrent fusion between the gene KLK4 and the pseudogene KLKP1. This was the first time such a fusion involving a pseudogene was identified in any cancer type.• Development of diagnostic tools: Palanisamy developed advanced methods like Fluorescence In Situ Hybridization (FISH) probes for routine cancer diagnosis, particularly for detecting recurrent chromosomal translocations, which are hallmarks of several cancers. This work was supported by grants from the National Cancer Institute (NCI) and resulted in patents for his innovative approaches.• Novel molecular profiling of prostate cancer: He pioneered approaches that revealed new subsets of prostate cancer, including those with dual ERG/SPINK1 rearrangements or dual ETS rearrangements involving ERG and ETV1 in distinct tumor foci.• Extensive publications and presentations: Palanisamy has authored over 150 peer-reviewed publications and delivered numerous presentations at cancer research conferences, sharing his findings with the scientific community.• Leadership and institutional contributions: Palanisamy served as Group Leader of Cancer Biology at the Genome Institute of Singapore, where he established a molecular cytogenetics laboratory. He also held a role as Director of Research and Development at Cancer Genetics, Inc., where he focused on translating research discoveries into diagnostic tools for cancer patients. In essence, Palanisamy's work has significantly advanced the understanding of the molecular basis of cancers, particularly prostate cancer, leading to the identification of potential therapeutic targets and contributing to the development of improved diagnostic methods. His contributions have impacted the understanding and treatment of various cancers, including prostate cancer, melanoma, breast cancer, and gastric cancer. AwardsNallasivam Palanisamy: Awards and honors in cancer researchDr. Nallasivam Palanisamy, an expert in prostate cancer research, has received several awards and recognition for contributions to the understanding and treatment of cancer. His accolades include:• 2023 Bayer-PCF Health Equity Research Award: The Prostate Cancer Foundation, in partnership with Bayer, granted this award for the project "Molecular Evaluation of Prostate Saturation and Progression Biopsies for Risk Assessment and Early Intervention." This research analyzes prostate tumor samples from both Black and white patients to identify racial differences in prostate cancer biology and progression. The goal is to improve biomarker-based risk assessment tools for Black patients and reduce health disparities.• Senior Research Fellowship (SRF) Award: From 1987 to 1990, the Council of Scientific and Industrial Research (CSIR) in New Delhi, India, awarded him the Senior Research Fellowship (SRF). His work has been supported by significant grant funding, including over $2 million from the National Cancer Institute (NCI) through three Phase I and one Phase II SBIR grants. Palanisamy is recognized for contributions to cancer research, with over 150 peer-reviewed publications and presentations at scientific conferences. He holds patents for novel methods in developing Fluorescence In Situ Hybridization (FISH) probes for cancer diagnosis. He is a speaker at events, such as the Cancer Research Summit on January 30, 2025, and a member of organizations like the Society for Basic Urologic Research, the American Association for the Advancement of Sciences, and the American Association for Cancer Research. CollaboratorsNallasivam Palanisamy: Collaborators and affiliationsDr. Nallasivam Palanisamy collaborates with various researchers and institutions in his cancer research efforts. His collaborators include:Individuals• Sooryanarayana Varambally: Professor, Department of Pathology, University of Alabama at Birmingham.• Bushra Ateeq: Professor and Joy Gill Chair & Senior Fellow at DBT/Wellcome Trust, IIT Kanpur.• Shanker Kalyana-Sundaram: GlaxoSmithKline.• Ram S Mani: Associate Professor, University of Texas Southwestern Medical Center, Dallas.• Nilesh Gupta: Henry Ford Hospital.• Sean R Williamson: Cleveland Clinic.• Patrick Tan: Duke-NUS Medical School.• Sunitha Nagrath: Professor of Chemical Engineering, University of Michigan.• Dhananjay Chitale: Henry Ford Health System.• Riccardo Dalla Favera: Professor of Genetics, Columbia University.• Craig Rogers: Vattikuti Urology Institute, Henry Ford Hospital.• Tarek A Bismar: University of Calgary Cumming School of Medicine.• Mark A Rubin: Professor and Director, Department for BioMedical Research, University of Bern.• Edison T Liu: The Jackson Laboratory.• Mani Menon: Professor of Urology, Mount Sinai.• Kathleen Day: University of Michigan.• Leonard Lipovich: Adjunct Professor of Molecular Medicine and Genetics, School of Medicine, Wayne State University.• Wei Zhao: Department of Hematology/Oncology, Henry Ford Health.• Pin Li: Department of Public Health, Henry Ford Health.• Shannon Carskadon: Department of Urology, Henry Ford Health.• Sunita Ghosh: Department of Public Health, Henry Ford Health.• James Peabody: Department of Urology, Henry Ford Health.• Raju Chaganti: A key figure in Palanisamy's post-doctoral training and collaborations, including in developing FISH probes.• Arul M Chinnaiyan: Co-inventor of RAF Gene Fusions related patents. Institutions and organizations• Henry Ford Health System: Serves as an Associate Scientist in Urology, Department of Urology, Vattikuti Urology Institute.• University of Michigan: Holds an Adjunct Associate Professor position.• Michigan State University: Holds an Associate Professor position.• University of Alabama at Birmingham: Collaborates with researchers like Sooryanarayana Varambally.• University of Texas Southwestern Medical Center, Dallas: Collaborates with researchers like Ram S Mani.• DBT/Wellcome Trust, IIT Kanpur: Collaborates with researchers like Bushra Ateeq.• GlaxoSmithKline: Collaborates with researchers like Shanker Kalyana-Sundaram.• Ventana Medical Systems: A company with whom he has collaborated on projects like developing automated dual color immunohistochemistry procedures.• National Cancer Institute (NCI): His work has been supported by grants from the NCI.• The Prostate Cancer Foundation (PCF): Received an award for his work on prostate cancer and collaborates with them through grants.• Council of Scientific and Industrial Research (CSIR), New Delhi, India: Awarded him the Senior Research Fellowship (SRF).• Karmanos Cancer Institute, Wayne State University, Detroit, MI: Was a Member in 2015.• The Jackson Laboratory: Collaborates with researchers like Edison T Liu. In essence, Dr. Palanisamy's collaborations span a diverse range of academic and industrial institutions, reflecting a commitment to advancing cancer research through teamwork and a multidisciplinary approach.Publications with high impactNallasivam Palanisamy: High-impact publications in cancer researchDr. Nallasivam Palanisamy has authored or co-authored over 150 publications that have significantly impacted the field of cancer research, particularly in prostate cancer. Some of his most impactful publications include: • Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma: This highly cited paper, co-authored by Palanisamy, reported the discovery of recurrent RAF gene fusions in subsets of ETS-negative prostate cancer, as well as in gastric cancers and melanoma. This was a crucial finding because these RAF fusions are "druggable", suggesting that patients with these specific gene fusions might respond to RAF and MEK inhibitors already available. It opened doors for targeted therapies in specific cancer subsets and highlighted the potential of sequencing tumor transcriptomes and genomes to identify rare targetable fusions across cancer types. The findings were further elaborated in a Nature Reviews Urology article, emphasizing the potential for RAF kinase inhibitors in treating tumors with these fusions.• Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer: In this research, Palanisamy and his team identified a novel type of gene fusion involving a pseudogene, specifically a recurrent fusion between the gene KLK4 and the pseudogene KLKP1. This discovery was the first time a recurrent gene fusion associated with a pseudogene was identified in any cancer type. This fusion results in the conversion of the non-coding pseudogene into a protein-coding gene, with the resulting fusion protein detectable in patient urine samples. This offers a potential for non-invasive detection of high-Gleason grade prostate cancer.• Discovery of non-ETS gene fusions in human prostate cancer using next generation sequencing: This publication described the discovery of novel ETS and non-ETS prostate cancer fusions, further demonstrating that some of these fusions may act as additional drivers of tumor progression. It also provided insights into how ETS overexpression might predispose to specific DNA breakpoints, distinct from those seen in fusion-negative prostate cancers.• The landscape and therapeutic relevance of cancer-associated transcript fusions: This work described the landscape of transcript fusions across a large number of tumor samples and identified clinically relevant fusion events that were previously unrecognized. It suggests the potential for using kinase inhibitors in various tumor types, such as bladder carcinoma, glioblastoma, and lung adenocarcinoma, based on the presence of specific fusions. It also supports the concept of basket clinical trials, where patients are matched with experimental therapies based on their genomic profile rather than the tumor's origin.• Clonal evaluation of prostate cancer molecular heterogeneity in biopsy samples by dual immunohistochemistry and dual RNA in situ hybridization: This paper presented an approach for analyzing prostate cancer biopsies to understand tumor heterogeneity and identify distinct molecular subtypes. The study used dual immunohistochemistry and dual RNA in situ hybridization to analyze a large cohort of patients. This research has implications for defining dominant tumor nodules and understanding how different tumor areas might have varying molecular characteristics impacting prognosis and treatment strategies. These publications highlight Palanisamy's crucial contributions to understanding the molecular basis of cancer and his efforts to translate research discoveries into diagnostic tools and potential therapeutic strategies. How his contributions are compared to top cancer scientistsAssessing how Dr. Nallasivam Palanisamy's contributions compare to those of other top cancer scientists requires considering several factors. While directly ranking or quantitatively comparing scientists is challenging, based on the provided information, the nature and significance of his impact can be highlighted:High-impact discoveries in prostate cancer research• RAF Gene Fusion Discovery: Palanisamy's discovery of recurrent RAF gene fusions in prostate cancer is considered a significant advancement. These fusions are "druggable" targets, opening up new therapeutic avenues for specific prostate cancer subsets. This discovery aligns with the focus of many top cancer scientists on identifying actionable genetic alterations that can lead to personalized therapies.• Dr. Nallasivam Palanisamy's discoveries of RAF gene fusions have significant implications for prostate cancer treatment, particularly by expanding options for targeted therapy. His work identified a specific, "druggable" genetic target in a subset of prostate cancers, allowing for a more personalized and precise treatment approach, especially in cases where other common genetic drivers are absent. • Targeted therapy for a new subset of patients• Before Palanisamy's discovery, most gene fusion research in prostate cancer focused on the ETS family of transcription factors, which are difficult to target with drugs because they lack enzymatic activity. Palanisamy's research offered a new avenue for a specific patient population: • He identified RAF kinase gene fusions in a small but distinct subset of ETS-negative prostate cancers, meaning patients with these tumors could not be targeted with therapies aimed at the ETS gene.• Unlike ETS fusions, RAF kinase fusions result in an active enzyme that can be inhibited by existing drugs. • Use of existing RAF/MEK inhibitors• Palanisamy's early work demonstrated that RAF fusions—specifically SLC45A3-BRAF and ESRP1-RAF1—made prostate cancer cells sensitive to drugs that inhibit the RAF and MEK signaling pathways. • Proof of concept: Laboratory studies on cells with these fusions showed that their abnormal growth was sensitive to sorafenib, an FDA-approved RAF inhibitor.• Direct clinical potential: This showed that screening patients for RAF fusions could identify those who may benefit from existing RAF-inhibitor drugs, similar to how ALK inhibitors are used for patients with certain types of lung cancer. • Improved diagnostic and risk stratification• Dr. Palanisamy's discoveries also have implications for how prostate cancer is diagnosed and classified. • Next-generation sequencing (NGS): His research highlights how advanced sequencing technologies are essential for detecting complex genetic changes, like gene fusions, that can guide clinical decisions.• Molecular subtyping: Identifying RAF fusions helps to classify prostate cancer into distinct molecular subtypes, moving away from a one-size-fits-all approach. This accounts for the significant genetic diversity, or heterogeneity, found within and between tumors. • Basis for future research and drug development• The discovery of "druggable" RAF fusions has opened the door for further advances: • Clinical trials: Palanisamy's work provided the rationale for clinical trials to test RAF-based therapies in patients with RAF-fusion-positive prostate cancer.• Broader application: His research into other novel biomarkers, including pseudogene-related fusions like KLK4-KLKP1, continues to expand the field of personalized medicine and non-invasive diagnostics for prostate cancer. • Pseudogene-Associated Gene Fusion: The identification of the first recurrent gene fusion involving a pseudogene, between KLK4 and KLKP1, is described as a game-changing discovery. The potential of this fusion protein as a non-invasive biomarker for high-grade prostate cancer suggests a significant impact on diagnostics. This discovery showcases an innovative approach to exploring the less-understood regions of the genome for cancer insights. • In addition to the RAF gene fusions, Dr. Nallasivam Palanisamy's research has identified other significant gene fusions in prostate cancer, including a groundbreaking finding of a recurrent gene fusion involving a non-coding pseudogene. • KLK4-KLKP1 fusion• Palanisamy and his team identified a novel gene fusion that combines the protein-coding gene KLK4 with the non-coding pseudogene KLKP1. • Pseudogene research: This was the first time a recurrent gene fusion involving a pseudogene had been found in any cancer. Pseudogenes were once considered "junk DNA," but Palanisamy's work demonstrated they can have functional importance in cancer development.• Unique protein: The fusion is unique because it causes the normally non-coding KLKP1 to become part of a new protein, with a new open reading frame. This creates a novel fusion protein involved in tumor progression.• Biomarker potential: The resulting fusion protein is prostate cancer-specific and can be detected in patient urine samples. This offers a non-invasive method for detecting high-grade prostate cancer and potentially tracking its progression, providing a more accurate biomarker than the standard PSA test. • Dual ETS/SPINK1 rearrangements• Dr. Palanisamy's work has also explored the complex genetic landscape of prostate cancer beyond single fusion events.• Dual rearrangements: He helped identify a subset of prostate cancers with complex molecular profiles, including tumors with both an ERG fusion and a SPINK1 rearrangement in separate tumor foci.• What's the clinical significance of dual ERG/SPINK1 rearrangements in prostate cancer?• While ERG fusions and SPINK1 overexpression are typically mutually exclusive in prostate cancer, the presence of dual ERG/SPINK1 rearrangements, though rare, carries significant clinical implications. In most cases, these dual-positive findings are indicative of heterogeneous or multi-clonal tumors rather than a single, co-expressing cancer focus. • Dual status indicates tumor heterogeneity• Distinct clones: Prostate cancer is often multifocal, meaning a patient can have multiple, genetically distinct tumors or clones within their prostate.• Collision tumors: A dual ERG/SPINK1 finding in a biopsy often indicates a "collision tumor," where an ERG-positive cancer clone and a SPINK1-positive cancer clone are found in close proximity.• Significance for biopsy: Pathologists can use dual-color immunohistochemistry (IHC) to assess if two separate tumor foci in a single biopsy core are genetically the same (concordant) or different (discordant). Discordant results confirm the existence of distinct, multi-clonal disease. • Association with aggressive disease• Higher-grade tumors: Research has shown that the rare co-expression of SPINK1 and ERG in the same tumor focus is associated with higher Gleason scores, suggesting that this particular combination may mark a more aggressive subpopulation of prostate cancer.• Metastasis risk: Studies have found a higher frequency of the dual ERG/SPINK1 phenotype in the primary tumors of patients who later develop lymph node metastases. This indicates that the subpopulation with the dual phenotype may be more likely to spread, though the expression can become downregulated in the metastatic site. • Implications for risk assessment• Inadequate sampling: The high degree of heterogeneity, especially of SPINK1 expression, can make it difficult to get a complete picture of the tumor's genetic makeup from a single biopsy. This suggests that without adequate sampling, a patient could have a more aggressive, dual-positive clone that is missed.• Refining prognosis: While initial studies showed conflicting results on SPINK1's prognostic value for localized tumors, its association with higher Gleason grade and metastatic risk in the dual-positive context supports the use of dual-status analysis for better risk stratification. • Impact on treatment decisions• Challenges for targeted therapy: The dual-positive status complicates treatment strategies that might be developed for ERG-driven or SPINK1-driven cancers individually. For example, a treatment designed for a pure ERG-positive cancer would likely be ineffective against the SPINK1-positive clone, and vice-versa.• Potential for resistance: The presence of different clones in the same tumor could also contribute to treatment resistance, as one subpopulation might evade a therapy that eliminates the other. This underlines the need for broader treatment approaches that can address the full scope of tumor heterogeneity. • Mutually exclusive expression: His research on the KLK4-KLKP1 fusion also revealed its expression pattern relative to other gene abnormalities. He found that KLK4-KLKP1 expression occurs alongside ERG fusions but is mutually exclusive with SPINK1 and other ETS fusions (ETV1, ETV4, and ETV5). • Androgen-regulated gene fusions• Palanisamy's research has also contributed to the understanding of how gene fusions are created in the first place, identifying a link to hormone signaling. • SLC45A3-ELK4: His work investigated the expression of the transcription-induced chimeric RNA SLC45A3-ELK4.• Chromosomal proximity: Studies involving Palanisamy showed that hormones like androgen can cause chromosomes to relocate near each other in 3D space, making them vulnerable to breaks and subsequent fusion events when cells are under stress. Bridging research and clinical applications• Diagnostic Tools: Palanisamy's efforts to develop and commercialize FISH probes for routine cancer diagnosis demonstrate a commitment to translating research findings into practical clinical tools. This is a hallmark of top cancer scientists who aim to improve patient care through their discoveries.• Targeting Racial Disparities: His work exploring racial disparities in prostate cancer and the molecular differences between African American and European American patients highlights a focus on addressing health equity in cancer care, a crucial area of research for many leading scientists. Collaborative and leadership roles• Collaboration: His extensive network of collaborators across various institutions showcases an ability to work within a broader scientific community, a trait often seen in influential researchers.• Leadership Positions: His roles as Group Leader at the Genome Institute of Singapore and Director of Research and Development at Cancer Genetics, Inc. demonstrate leadership skills and an ability to guide research toward tangible outcomes. Recognition and impact• Publications and Citations: Having over 150 peer-reviewed publications, including in high-impact journals, and being recognized in the top 3% of world scientists, indicate a strong presence and influence in the scientific community.• Awards: The Prostate Cancer Foundation award, in partnership with Bayer, further validates the importance and potential impact of his research on health equity in prostate cancer. Comparison with other scientistsMany top cancer scientists focus on specific cancer types, molecular mechanisms, or therapeutic approaches. Palanisamy's contributions can be seen as significant within the field of prostate cancer and cancer genomics. His work on RAF fusions and pseudogene-associated fusions represents fundamental discoveries that have the potential to impact diagnosis and treatment strategies. However, comparing his overall contributions to those of all "top cancer scientists" would require a comprehensive analysis across numerous areas of cancer research, considering factors like the breadth of impact across different cancer types, the number of successful clinical applications, and the overall paradigm shifts driven by their work. In conclusion, Dr. Palanisamy is a prominent cancer researcher with notable contributions in understanding the molecular basis of prostate cancer and translating those insights into potential diagnostic and therapeutic strategies. His work on gene fusions and pseudogenes is considered particularly impactful within his specialized areas of research. This is for informational purposes only. For medical advice or diagnosis, consult a professional. AI responses may include mistakes. Predict his future career growthNallasivam Palanisamy's future career growth is likely to involve a deepening focus on cancer genomics and precision medicine, with a strong emphasis on translational research that bridges the gap between laboratory discoveries and clinical applications. Based on his track record, expertise, and the evolving landscape of cancer research, several areas suggest potential for significant future growth: 1. Expanding and refining gene fusion research• Palanisamy has already made key discoveries in gene fusions, including RAF kinase fusions and pseudogene-associated fusions. His future work will likely continue to expand on this, identifying novel gene fusions across various cancer types and further elucidating their roles in disease development and progression.• The ultimate goal is to translate these discoveries into clinically actionable insights. This may involve developing more specific diagnostic tools and exploring targeted therapies that are tailored to patients with specific gene fusions. The discovery of RAF gene fusions being "druggable" already points in this direction. 2. Leveraging next-generation sequencing and big data• Palanisamy's research relies heavily on next-generation sequencing technology for transcriptome sequencing, gene fusion detection, and integrated genomic analysis. His future career growth will likely involve harnessing the rapidly evolving field of big data and advanced bioinformatics to analyze complex genomic data sets, enabling a more comprehensive understanding of cancer's genetic complexity. 3. Advancing precision medicine and personalized oncology• With the increasing relevance of genomics in clinical cancer care, Palanisamy's expertise in identifying novel biomarkers and understanding the molecular mechanisms of treatment will be crucial.• His work on racial disparities in prostate cancer, aiming to improve biomarker-based risk assessment for Black patients, exemplifies his contribution to equitable, personalized care. This focus on reducing health disparities within the context of precision medicine is likely to gain increasing prominence. 4. Collaborative research and leadership in translational science• Palanisamy's extensive collaborations with researchers and institutions highlight his ability to work effectively in a multidisciplinary environment. As cancer research becomes more complex, requiring expertise across various fields, his collaborative approach will likely continue to be a significant asset.• With his experience as a Group Leader and Director of Research and Development, he is well-positioned for further leadership roles that emphasize translating scientific discoveries into clinical applications. Potential challengesDespite these opportunities, challenges remain:• The complexity of cancer biology: Understanding the intricacies of cancer at the molecular level continues to be a significant challenge.• Translating discoveries into clinical practice: Moving from laboratory findings to approved diagnostic tools and therapies can be a lengthy and challenging process.• Cost and accessibility: Ensuring that advanced genomic testing and personalized therapies are affordable and accessible to all patients, particularly in lower-income settings, remains a critical hurdle. What other cancers has Dr. Palanisamy studied regarding gene fusions?In addition to his primary focus on prostate cancer, Dr. Nallasivam Palanisamy's research on gene fusions has extended to other cancer types, including:• Melanoma: His research has identified RAF kinase gene fusions in some melanoma cases. These discoveries have potential implications for developing targeted therapies for melanoma patients with these fusions, notes Bio-Techne.• Gastric Cancer: RAF kinase gene fusions were also found in gastric cancer, says Bio-Techne.• Lymphoma: Early in his career, during a post-doctoral research fellowship, he focused on discovering and characterizing gene fusions in lymphoma and multiple myeloma. His work identified IGH/PAX5, IGH/MUC1, IGH/FGFR2B, IGH/CHST11, IGH/IRTA1, and IGH/IRTA2 fusion genes.• Kidney Cancer: Dr. Palanisamy has been involved in collaborative projects concerning kidney cancer.• Bladder Cancer: He has also participated in collaborative projects involving bladder cancer. This indicates that while prostate cancer remains his primary area of expertise, he has broadened his research to understand the role of gene fusions in other types of cancer. His findings suggest that the use of next-generation sequencing (NGS) technology to analyze the genome-wide expression may lead to the discovery of pseudogene-associated biomarkers in other cancers, according to SelectScience.
Overall, Nallasivam Palanisamy's proven track record, expertise in cutting-edge genomic technologies, and strong focus on translational research position him for continued career growth and impact in the field of cancer research, particularly in the realm of precision medicine and the development of targeted therapies. His work on gene fusions and racial disparities in prostate cancer has the potential to significantly improve patient care and advance the understanding of cancer biology.
What pseudogenes did Dr. Palanisamy identify as potential prostate cancer biomarkers?Dr. Nallasivam Palanisamy's research has identified KLKP1 as a significant pseudogene associated with a recurrent gene fusion in prostate cancer. More specifically, Dr. Palanisamy's team discovered the KLK4-KLKP1 fusion gene, where the protein-coding gene KLK4 fuses with the noncoding pseudogene KLKP1. This fusion is noteworthy because it converts the noncoding KLKP1 pseudogene into a protein-coding gene. Furthermore, Dr. Palanisamy's research identified 8 pseudogenes that were expressed in prostate cancer tissue but not in normal prostate tissue. While the specific names of all 8 are not explicitly listed in the provided snippets, the discovery of this set of pseudogenes opens up possibilities for new prostate cancer biomarkers beyond the well-known KLK4-KLKP1 fusion. How does KLK4-KLKP1 fusion convert KLKP1 into a protein-coding gene?The KLK4-KLKP1 fusion converts the normally non-coding KLKP1 pseudogene into a protein-coding gene through a specific genomic rearrangement that effectively merges the protein-coding KLK4 gene with the pseudogene KLKP1. Here's a breakdown of the likely mechanism: 1. Gene Fusion Event: A genomic rearrangement occurs, leading to the fusion of a portion of the KLK4 gene with a portion of the KLKP1 pseudogene.2. Conversion to a Protein-Coding Gene: The resulting fusion gene effectively places the coding sequence of the KLKP1 pseudogene under the control of the KLK4 regulatory elements (e.g., promoter, enhancers) that drive gene expression.3. Frame Shift: The fusion process can cause a shift in the open reading frame of the KLKP1 pseudogene, allowing it to be translated into a protein. The resulting chimeric sequence predicts a 164-amino acid protein, of which the latter third (55 amino acids) is derived from KLKP1, as stated in a study published in ScienceDirect.com.4. Novel Protein Production: This process results in the production of a novel chimeric protein that incorporates elements from both KLK4 and KLKP1. In essence, the fusion bypasses the normal mechanisms that silence pseudogenes, allowing the KLKP1 sequence to be transcribed and translated into a functional protein within the context of the KLK4-KLKP1 fusion gene. This is a rare example where gene fusion directly leads to the conversion of a noncoding pseudogene to a protein-coding gene.
Nallasivam Palanisamy is an accomplished cancer researcher specializing in prostate cancer, cancer genomics, and molecular pathology. He currently serves as an Associate Scientist in the Department of Urology at Henry Ford Health and an Adjunct Associate Professor at Michigan State University.
Key contributions
• Discovery of RAF gene fusions and pseudogene-associated gene fusions in prostate cancer using next-generation sequencing.
• Pioneering work in developing novel biomarkers for diagnosing and treating prostate cancer.
• Successfully applying next-generation sequencing for transcriptome sequencing to discover new recurrent gene fusions in various cancers.
• Identifying novel approaches in FISH probe development for diagnosing recurrent chromosome translocations in cancer.
Professional background
Nallasivam Palanisamy has held positions such as Research Assistant Professor at the Michigan Center for Translational Pathology, Group Leader of Cancer Biology at the Genome Institute of Singapore, Adjunct Assistant Professor at Nanyang Technological University, and Founding Director of Research and Development at Cancer Genetics Inc.
Education
Palanisamy earned B.Sc., M.Sc., M.Phil., and Ph.D. degrees in Genetics from the University of Madras and completed postdoctoral research at the University of Michigan and the University of Vermont.
Recognition and achievements
His work includes authoring over 150 peer-reviewed publications and holding five patents. He has also received significant research funding and has been an invited speaker at various events. Colleagues have praised his expertise in cancer research.
Career accomplishments
Nallasivam Palanisamy: Career accomplishments in cancer research
Dr. Nallasivam Palanisamy is a distinguished Associate Scientist in Urology at Henry Ford Health and an Adjunct Associate Professor at the University of Michigan, specializing in the molecular underpinnings of cancer, particularly prostate cancer.
His career achievements include:
• Discovery of RAF gene fusions: Palanisamy discovered recurrent RAF gene fusions in prostate cancer cases that were negative for the typical ETS gene rearrangements. He also identified these rearrangements in some cases of melanoma and gastric cancers. This discovery is crucial because RAF gene fusions are "druggable," meaning they can be targeted with existing medications like BRAF and MEK inhibitors, opening doors for targeted therapies in specific cancer subsets.
• Identification of Pseudogene-Associated Gene Fusions: He also made a significant breakthrough by identifying a novel type of gene fusion involving a pseudogene, specifically a recurrent fusion between the gene KLK4 and the pseudogene KLKP1. This was the first time such a fusion involving a pseudogene was identified in any cancer type.
• Development of diagnostic tools: Palanisamy developed advanced methods like Fluorescence In Situ Hybridization (FISH) probes for routine cancer diagnosis, particularly for detecting recurrent chromosomal translocations, which are hallmarks of several cancers. This work was supported by grants from the National Cancer Institute (NCI) and resulted in patents for his innovative approaches.
• Novel molecular profiling of prostate cancer: He pioneered approaches that revealed new subsets of prostate cancer, including those with dual ERG/SPINK1 rearrangements or dual ETS rearrangements involving ERG and ETV1 in distinct tumor foci.
• Extensive publications and presentations: Palanisamy has authored over 150 peer-reviewed publications and delivered numerous presentations at cancer research conferences, sharing his findings with the scientific community.
• Leadership and institutional contributions: Palanisamy served as Group Leader of Cancer Biology at the Genome Institute of Singapore, where he established a molecular cytogenetics laboratory. He also held a role as Director of Research and Development at Cancer Genetics, Inc., where he focused on translating research discoveries into diagnostic tools for cancer patients.
In essence, Palanisamy's work has significantly advanced the understanding of the molecular basis of cancers, particularly prostate cancer, leading to the identification of potential therapeutic targets and contributing to the development of improved diagnostic methods. His contributions have impacted the understanding and treatment of various cancers, including prostate cancer, melanoma, breast cancer, and gastric cancer.
Awards
Nallasivam Palanisamy: Awards and honors in cancer research
Dr. Nallasivam Palanisamy, an expert in prostate cancer research, has received several awards and recognition for contributions to the understanding and treatment of cancer. His accolades include:
• 2023 Bayer-PCF Health Equity Research Award: The Prostate Cancer Foundation, in partnership with Bayer, granted this award for the project "Molecular Evaluation of Prostate Saturation and Progression Biopsies for Risk Assessment and Early Intervention." This research analyzes prostate tumor samples from both Black and white patients to identify racial differences in prostate cancer biology and progression. The goal is to improve biomarker-based risk assessment tools for Black patients and reduce health disparities.
• Senior Research Fellowship (SRF) Award: From 1987 to 1990, the Council of Scientific and Industrial Research (CSIR) in New Delhi, India, awarded him the Senior Research Fellowship (SRF).
His work has been supported by significant grant funding, including over $2 million from the National Cancer Institute (NCI) through three Phase I and one Phase II SBIR grants.
Palanisamy is recognized for contributions to cancer research, with over 150 peer-reviewed publications and presentations at scientific conferences. He holds patents for novel methods in developing Fluorescence In Situ Hybridization (FISH) probes for cancer diagnosis. He is a speaker at events, such as the Cancer Research Summit on January 30, 2025, and a member of organizations like the Society for Basic Urologic Research, the American Association for the Advancement of Sciences, and the American Association for Cancer Research.
Collaborators
Nallasivam Palanisamy: Collaborators and affiliations
Dr. Nallasivam Palanisamy collaborates with various researchers and institutions in his cancer research efforts. His collaborators include:
Individuals
• Sooryanarayana Varambally: Professor, Department of Pathology, University of Alabama at Birmingham.
• Bushra Ateeq: Professor and Joy Gill Chair & Senior Fellow at DBT/Wellcome Trust, IIT Kanpur.
• Shanker Kalyana-Sundaram: GlaxoSmithKline.
• Ram S Mani: Associate Professor, University of Texas Southwestern Medical Center, Dallas.
• Nilesh Gupta: Henry Ford Hospital.
• Sean R Williamson: Cleveland Clinic.
• Patrick Tan: Duke-NUS Medical School.
• Sunitha Nagrath: Professor of Chemical Engineering, University of Michigan.
• Dhananjay Chitale: Henry Ford Health System.
• Riccardo Dalla Favera: Professor of Genetics, Columbia University.
• Craig Rogers: Vattikuti Urology Institute, Henry Ford Hospital.
• Tarek A Bismar: University of Calgary Cumming School of Medicine.
• Mark A Rubin: Professor and Director, Department for BioMedical Research, University of Bern.
• Edison T Liu: The Jackson Laboratory.
• Mani Menon: Professor of Urology, Mount Sinai.
• Kathleen Day: University of Michigan.
• Leonard Lipovich: Adjunct Professor of Molecular Medicine and Genetics, School of Medicine, Wayne State University.
• Wei Zhao: Department of Hematology/Oncology, Henry Ford Health.
• Pin Li: Department of Public Health, Henry Ford Health.
• Shannon Carskadon: Department of Urology, Henry Ford Health.
• Sunita Ghosh: Department of Public Health, Henry Ford Health.
• James Peabody: Department of Urology, Henry Ford Health.
• Raju Chaganti: A key figure in Palanisamy's post-doctoral training and collaborations, including in developing FISH probes.
• Arul M Chinnaiyan: Co-inventor of RAF Gene Fusions related patents.
Institutions and organizations
• Henry Ford Health System: Serves as an Associate Scientist in Urology, Department of Urology, Vattikuti Urology Institute.
• University of Michigan:
Holds an Adjunct Associate Professor position.
• Michigan State University:
Holds an Associate Professor position.
• University of Alabama at Birmingham:
Collaborates with researchers like Sooryanarayana Varambally.
• University of Texas Southwestern Medical Center, Dallas: Collaborates with researchers like Ram S Mani.
• DBT/Wellcome Trust, IIT Kanpur: Collaborates with researchers like Bushra Ateeq.
• GlaxoSmithKline: Collaborates with researchers like Shanker Kalyana-Sundaram.
• Ventana Medical Systems: A company with whom he has collaborated on projects like developing automated dual color immunohistochemistry procedures.
• National Cancer Institute (NCI): His work has been supported by grants from the NCI.
• The Prostate Cancer Foundation (PCF): Received an award for his work on prostate cancer and collaborates with them through grants.
• Council of Scientific and Industrial Research (CSIR), New Delhi, India: Awarded him the Senior Research Fellowship (SRF).
• Karmanos Cancer Institute, Wayne State University, Detroit, MI: Was a Member in 2015.
• The Jackson Laboratory: Collaborates with researchers like Edison T Liu.
In essence, Dr. Palanisamy's collaborations span a diverse range of academic and industrial institutions, reflecting a commitment to advancing cancer research through teamwork and a multidisciplinary approach.
Publications with high impact
Nallasivam Palanisamy: High-impact publications in cancer research
Dr. Nallasivam Palanisamy has authored or co-authored over 150 publications that have significantly impacted the field of cancer research, particularly in prostate cancer. Some of his most impactful publications include:
• Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma: This highly cited paper, co-authored by Palanisamy, reported the discovery of recurrent RAF gene fusions in subsets of ETS-negative prostate cancer, as well as in gastric cancers and melanoma. This was a crucial finding because these RAF fusions are "druggable", suggesting that patients with these specific gene fusions might respond to RAF and MEK inhibitors already available. It opened doors for targeted therapies in specific cancer subsets and highlighted the potential of sequencing tumor transcriptomes and genomes to identify rare targetable fusions across cancer types. The findings were further elaborated in a Nature Reviews Urology article, emphasizing the potential for RAF kinase inhibitors in treating tumors with these fusions.
• Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer: In this research, Palanisamy and his team identified a novel type of gene fusion involving a pseudogene, specifically a recurrent fusion between the gene KLK4 and the pseudogene KLKP1. This discovery was the first time a recurrent gene fusion associated with a pseudogene was identified in any cancer type. This fusion results in the conversion of the non-coding pseudogene into a protein-coding gene, with the resulting fusion protein detectable in patient urine samples. This offers a potential for non-invasive detection of high-Gleason grade prostate cancer.
• Discovery of non-ETS gene fusions in human prostate cancer using next generation sequencing: This publication described the discovery of novel ETS and non-ETS prostate cancer fusions, further demonstrating that some of these fusions may act as additional drivers of tumor progression. It also provided insights into how ETS overexpression might predispose to specific DNA breakpoints, distinct from those seen in fusion-negative prostate cancers.
• The landscape and therapeutic relevance of cancer-associated transcript fusions: This work described the landscape of transcript fusions across a large number of tumor samples and identified clinically relevant fusion events that were previously unrecognized. It suggests the potential for using kinase inhibitors in various tumor types, such as bladder carcinoma, glioblastoma, and lung adenocarcinoma, based on the presence of specific fusions. It also supports the concept of basket clinical trials, where patients are matched with experimental therapies based on their genomic profile rather than the tumor's origin.
• Clonal evaluation of prostate cancer molecular heterogeneity in biopsy samples by dual immunohistochemistry and dual RNA in situ hybridization: This paper presented an approach for analyzing prostate cancer biopsies to understand tumor heterogeneity and identify distinct molecular subtypes. The study used dual immunohistochemistry and dual RNA in situ hybridization to analyze a large cohort of patients. This research has implications for defining dominant tumor nodules and understanding how different tumor areas might have varying molecular characteristics impacting prognosis and treatment strategies.
These publications highlight Palanisamy's crucial contributions to understanding the molecular basis of cancer and his efforts to translate research discoveries into diagnostic tools and potential therapeutic strategies.
How his contributions are compared to top cancer scientists
Assessing how Dr. Nallasivam Palanisamy's contributions compare to those of other top cancer scientists requires considering several factors. While directly ranking or quantitatively comparing scientists is challenging, based on the provided information, the nature and significance of his impact can be highlighted:
High-impact discoveries in prostate cancer research
• RAF Gene Fusion Discovery: Palanisamy's discovery of recurrent RAF gene fusions in prostate cancer is considered a significant advancement. These fusions are "druggable" targets, opening up new therapeutic avenues for specific prostate cancer subsets. This discovery aligns with the focus of many top cancer scientists on identifying actionable genetic alterations that can lead to personalized therapies.
• Dr. Nallasivam Palanisamy's discoveries of RAF gene fusions have significant implications for prostate cancer treatment, particularly by expanding options for targeted therapy. His work identified a specific, "druggable" genetic target in a subset of prostate cancers, allowing for a more personalized and precise treatment approach, especially in cases where other common genetic drivers are absent.
• Targeted therapy for a new subset of patients
• Before Palanisamy's discovery, most gene fusion research in prostate cancer focused on the ETS family of transcription factors, which are difficult to target with drugs because they lack enzymatic activity. Palanisamy's research offered a new avenue for a specific patient population:
• He identified RAF kinase gene fusions in a small but distinct subset of ETS-negative prostate cancers, meaning patients with these tumors could not be targeted with therapies aimed at the ETS gene.
• Unlike ETS fusions, RAF kinase fusions result in an active enzyme that can be inhibited by existing drugs.
• Use of existing RAF/MEK inhibitors
• Palanisamy's early work demonstrated that RAF fusions—specifically SLC45A3-BRAF and ESRP1-RAF1—made prostate cancer cells sensitive to drugs that inhibit the RAF and MEK signaling pathways.
• Proof of concept: Laboratory studies on cells with these fusions showed that their abnormal growth was sensitive to sorafenib, an FDA-approved RAF inhibitor.
• Direct clinical potential: This showed that screening patients for RAF fusions could identify those who may benefit from existing RAF-inhibitor drugs, similar to how ALK inhibitors are used for patients with certain types of lung cancer.
• Improved diagnostic and risk stratification
• Dr. Palanisamy's discoveries also have implications for how prostate cancer is diagnosed and classified.
• Next-generation sequencing (NGS): His research highlights how advanced sequencing technologies are essential for detecting complex genetic changes, like gene fusions, that can guide clinical decisions.
• Molecular subtyping: Identifying RAF fusions helps to classify prostate cancer into distinct molecular subtypes, moving away from a one-size-fits-all approach. This accounts for the significant genetic diversity, or heterogeneity, found within and between tumors.
• Basis for future research and drug development
• The discovery of "druggable" RAF fusions has opened the door for further advances:
• Clinical trials: Palanisamy's work provided the rationale for clinical trials to test RAF-based therapies in patients with RAF-fusion-positive prostate cancer.
• Broader application: His research into other novel biomarkers, including pseudogene-related fusions like KLK4-KLKP1, continues to expand the field of personalized medicine and non-invasive diagnostics for prostate cancer.
• Pseudogene-Associated Gene Fusion: The identification of the first recurrent gene fusion involving a pseudogene, between KLK4 and KLKP1, is described as a game-changing discovery. The potential of this fusion protein as a non-invasive biomarker for high-grade prostate cancer suggests a significant impact on diagnostics. This discovery showcases an innovative approach to exploring the less-understood regions of the genome for cancer insights.
• In addition to the RAF gene fusions, Dr. Nallasivam Palanisamy's research has identified other significant gene fusions in prostate cancer, including a groundbreaking finding of a recurrent gene fusion involving a non-coding pseudogene.
• KLK4-KLKP1 fusion
• Palanisamy and his team identified a novel gene fusion that combines the protein-coding gene KLK4 with the non-coding pseudogene KLKP1.
• Pseudogene research: This was the first time a recurrent gene fusion involving a pseudogene had been found in any cancer. Pseudogenes were once considered "junk DNA," but Palanisamy's work demonstrated they can have functional importance in cancer development.
• Unique protein: The fusion is unique because it causes the normally non-coding KLKP1 to become part of a new protein, with a new open reading frame. This creates a novel fusion protein involved in tumor progression.
• Biomarker potential: The resulting fusion protein is prostate cancer-specific and can be detected in patient urine samples. This offers a non-invasive method for detecting high-grade prostate cancer and potentially tracking its progression, providing a more accurate biomarker than the standard PSA test.
• Dual ETS/SPINK1 rearrangements
• Dr. Palanisamy's work has also explored the complex genetic landscape of prostate cancer beyond single fusion events.
• Dual rearrangements: He helped identify a subset of prostate cancers with complex molecular profiles, including tumors with both an ERG fusion and a SPINK1 rearrangement in separate tumor foci.
• What's the clinical significance of dual ERG/SPINK1 rearrangements in prostate cancer?
• While ERG fusions and SPINK1 overexpression are typically mutually exclusive in prostate cancer, the presence of dual ERG/SPINK1 rearrangements, though rare, carries significant clinical implications. In most cases, these dual-positive findings are indicative of heterogeneous or multi-clonal tumors rather than a single, co-expressing cancer focus.
• Dual status indicates tumor heterogeneity
• Distinct clones: Prostate cancer is often multifocal, meaning a patient can have multiple, genetically distinct tumors or clones within their prostate.
• Collision tumors: A dual ERG/SPINK1 finding in a biopsy often indicates a "collision tumor," where an ERG-positive cancer clone and a SPINK1-positive cancer clone are found in close proximity.
• Significance for biopsy: Pathologists can use dual-color immunohistochemistry (IHC) to assess if two separate tumor foci in a single biopsy core are genetically the same (concordant) or different (discordant). Discordant results confirm the existence of distinct, multi-clonal disease.
• Association with aggressive disease
• Higher-grade tumors: Research has shown that the rare co-expression of SPINK1 and ERG in the same tumor focus is associated with higher Gleason scores, suggesting that this particular combination may mark a more aggressive subpopulation of prostate cancer.
• Metastasis risk: Studies have found a higher frequency of the dual ERG/SPINK1 phenotype in the primary tumors of patients who later develop lymph node metastases. This indicates that the subpopulation with the dual phenotype may be more likely to spread, though the expression can become downregulated in the metastatic site.
• Implications for risk assessment
• Inadequate sampling: The high degree of heterogeneity, especially of SPINK1 expression, can make it difficult to get a complete picture of the tumor's genetic makeup from a single biopsy. This suggests that without adequate sampling, a patient could have a more aggressive, dual-positive clone that is missed.
• Refining prognosis: While initial studies showed conflicting results on SPINK1's prognostic value for localized tumors, its association with higher Gleason grade and metastatic risk in the dual-positive context supports the use of dual-status analysis for better risk stratification.
• Impact on treatment decisions
• Challenges for targeted therapy: The dual-positive status complicates treatment strategies that might be developed for ERG-driven or SPINK1-driven cancers individually. For example, a treatment designed for a pure ERG-positive cancer would likely be ineffective against the SPINK1-positive clone, and vice-versa.
• Potential for resistance: The presence of different clones in the same tumor could also contribute to treatment resistance, as one subpopulation might evade a therapy that eliminates the other. This underlines the need for broader treatment approaches that can address the full scope of tumor heterogeneity.
• Mutually exclusive expression: His research on the KLK4-KLKP1 fusion also revealed its expression pattern relative to other gene abnormalities. He found that KLK4-KLKP1 expression occurs alongside ERG fusions but is mutually exclusive with SPINK1 and other ETS fusions (ETV1, ETV4, and ETV5).
• Androgen-regulated gene fusions
• Palanisamy's research has also contributed to the understanding of how gene fusions are created in the first place, identifying a link to hormone signaling.
• SLC45A3-ELK4: His work investigated the expression of the transcription-induced chimeric RNA SLC45A3-ELK4.
• Chromosomal proximity: Studies involving Palanisamy showed that hormones like androgen can cause chromosomes to relocate near each other in 3D space, making them vulnerable to breaks and subsequent fusion events when cells are under stress.
Bridging research and clinical applications
• Diagnostic Tools: Palanisamy's efforts to develop and commercialize FISH probes for routine cancer diagnosis demonstrate a commitment to translating research findings into practical clinical tools. This is a hallmark of top cancer scientists who aim to improve patient care through their discoveries.
• Targeting Racial Disparities: His work exploring racial disparities in prostate cancer and the molecular differences between African American and European American patients highlights a focus on addressing health equity in cancer care, a crucial area of research for many leading scientists.
Collaborative and leadership roles
• Collaboration: His extensive network of collaborators across various institutions showcases an ability to work within a broader scientific community, a trait often seen in influential researchers.
• Leadership Positions: His roles as Group Leader at the Genome Institute of Singapore and Director of Research and Development at Cancer Genetics, Inc. demonstrate leadership skills and an ability to guide research toward tangible outcomes.
Recognition and impact
• Publications and Citations: Having over 150 peer-reviewed publications, including in high-impact journals, and being recognized in the top 3% of world scientists, indicate a strong presence and influence in the scientific community.
• Awards: The Prostate Cancer Foundation award, in partnership with Bayer, further validates the importance and potential impact of his research on health equity in prostate cancer.
Comparison with other scientists
Many top cancer scientists focus on specific cancer types, molecular mechanisms, or therapeutic approaches. Palanisamy's contributions can be seen as significant within the field of prostate cancer and cancer genomics. His work on RAF fusions and pseudogene-associated fusions represents fundamental discoveries that have the potential to impact diagnosis and treatment strategies. However, comparing his overall contributions to those of all "top cancer scientists" would require a comprehensive analysis across numerous areas of cancer research, considering factors like the breadth of impact across different cancer types, the number of successful clinical applications, and the overall paradigm shifts driven by their work.
In conclusion, Dr. Palanisamy is a prominent cancer researcher with notable contributions in understanding the molecular basis of prostate cancer and translating those insights into potential diagnostic and therapeutic strategies. His work on gene fusions and pseudogenes is considered particularly impactful within his specialized areas of research.
This is for informational purposes only. For medical advice or diagnosis, consult a professional. AI responses may include mistakes.
Predict his future career growth
Nallasivam Palanisamy's future career growth is likely to involve a deepening focus on cancer genomics and precision medicine, with a strong emphasis on translational research that bridges the gap between laboratory discoveries and clinical applications
. Based on his track record, expertise, and the evolving landscape of cancer research, several areas suggest potential for significant future growth:
1. Expanding and refining gene fusion research
• Palanisamy has already made key discoveries in gene fusions, including RAF kinase fusions and pseudogene-associated fusions. His future work will likely continue to expand on this, identifying novel gene fusions across various cancer types and further elucidating their roles in disease development and progression.
• The ultimate goal is to translate these discoveries into clinically actionable insights. This may involve developing more specific diagnostic tools and exploring targeted therapies that are tailored to patients with specific gene fusions. The discovery of RAF gene fusions being "druggable" already points in this direction.
2. Leveraging next-generation sequencing and big data
• Palanisamy's research relies heavily on next-generation sequencing technology for transcriptome sequencing, gene fusion detection, and integrated genomic analysis. His future career growth will likely involve harnessing the rapidly evolving field of big data and advanced bioinformatics to analyze complex genomic data sets, enabling a more comprehensive understanding of cancer's genetic complexity.
3. Advancing precision medicine and personalized oncology
• With the increasing relevance of genomics in clinical cancer care, Palanisamy's expertise in identifying novel biomarkers and understanding the molecular mechanisms of treatment will be crucial.
• His work on racial disparities in prostate cancer, aiming to improve biomarker-based risk assessment for Black patients, exemplifies his contribution to equitable, personalized care. This focus on reducing health disparities within the context of precision medicine is likely to gain increasing prominence.
4. Collaborative research and leadership in translational science
• Palanisamy's extensive collaborations with researchers and institutions highlight his ability to work effectively in a multidisciplinary environment. As cancer research becomes more complex, requiring expertise across various fields, his collaborative approach will likely continue to be a significant asset.
• With his experience as a Group Leader and Director of Research and Development, he is well-positioned for further leadership roles that emphasize translating scientific discoveries into clinical applications.
Potential challenges
Despite these opportunities, challenges remain:
• The complexity of cancer biology: Understanding the intricacies of cancer at the molecular level continues to be a significant challenge.
• Translating discoveries into clinical practice: Moving from laboratory findings to approved diagnostic tools and therapies can be a lengthy and challenging process.
• Cost and accessibility: Ensuring that advanced genomic testing and personalized therapies are affordable and accessible to all patients, particularly in lower-income settings, remains a critical hurdle.
What other cancers has Dr. Palanisamy studied regarding gene fusions?
In addition to his primary focus on prostate cancer, Dr. Nallasivam Palanisamy's research on gene fusions has extended to other cancer types, including:
• Melanoma: His research has identified RAF kinase gene fusions in some melanoma cases. These discoveries have potential implications for developing targeted therapies for melanoma patients with these fusions, notes Bio-Techne.
• Gastric Cancer: RAF kinase gene fusions were also found in gastric cancer, says Bio-Techne.
• Lymphoma: Early in his career, during a post-doctoral research fellowship, he focused on discovering and characterizing gene fusions in lymphoma and multiple myeloma. His work identified IGH/PAX5, IGH/MUC1, IGH/FGFR2B, IGH/CHST11, IGH/IRTA1, and IGH/IRTA2 fusion genes.
• Kidney Cancer: Dr. Palanisamy has been involved in collaborative projects concerning kidney cancer.
• Bladder Cancer: He has also participated in collaborative projects involving bladder cancer.
This indicates that while prostate cancer remains his primary area of expertise, he has broadened his research to understand the role of gene fusions in other types of cancer. His findings suggest that the use of next-generation sequencing (NGS) technology to analyze the genome-wide expression may lead to the discovery of pseudogene-associated biomarkers in other cancers, according to SelectScience.
Overall, Nallasivam Palanisamy's proven track record, expertise in cutting-edge genomic technologies, and strong focus on translational research position him for continued career growth and impact in the field of cancer research, particularly in the realm of precision medicine and the development of targeted therapies. His work on gene fusions and racial disparities in prostate cancer has the potential to significantly improve patient care and advance the understanding of cancer biology.
What pseudogenes did Dr. Palanisamy identify as potential prostate cancer biomarkers?
Dr. Nallasivam Palanisamy's research has identified
KLKP1 as a significant pseudogene associated with a recurrent gene fusion in prostate cancer.
More specifically, Dr. Palanisamy's team discovered the KLK4-KLKP1 fusion gene, where the protein-coding gene KLK4 fuses with the noncoding pseudogene KLKP1. This fusion is noteworthy because it converts the noncoding KLKP1 pseudogene into a protein-coding gene.
Furthermore, Dr. Palanisamy's research identified 8 pseudogenes that were expressed in prostate cancer tissue but not in normal prostate tissue. While the specific names of all 8 are not explicitly listed in the provided snippets, the discovery of this set of pseudogenes opens up possibilities for new prostate cancer biomarkers beyond the well-known KLK4-KLKP1 fusion.
How does KLK4-KLKP1 fusion convert KLKP1 into a protein-coding gene?
The KLK4-KLKP1 fusion converts the normally non-coding KLKP1 pseudogene into a protein-coding gene through a specific genomic rearrangement that effectively merges the protein-coding KLK4 gene with the pseudogene KLKP1
. Here's a breakdown of the likely mechanism:
1. Gene Fusion Event: A genomic rearrangement occurs, leading to the fusion of a portion of the KLK4 gene with a portion of the KLKP1 pseudogene.
2. Conversion to a Protein-Coding Gene: The resulting fusion gene effectively places the coding sequence of the KLKP1 pseudogene under the control of the KLK4 regulatory elements (e.g., promoter, enhancers) that drive gene expression.
3. Frame Shift: The fusion process can cause a shift in the open reading frame of the KLKP1 pseudogene, allowing it to be translated into a protein. The resulting chimeric sequence predicts a 164-amino acid protein, of which the latter third (55 amino acids) is derived from KLKP1, as stated in a study published in ScienceDirect.com.
4. Novel Protein Production: This process results in the production of a novel chimeric protein that incorporates elements from both KLK4 and KLKP1.
In essence, the fusion bypasses the normal mechanisms that silence pseudogenes, allowing the KLKP1 sequence to be transcribed and translated into a functional protein within the context of the KLK4-KLKP1 fusion gene. This is a rare example where gene fusion directly leads to the conversion of a noncoding pseudogene to a protein-coding gene.
