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Navonil De Sarkar, PhD

Navonil De Sarkar, PhD

Assistant Professor

Locations

  • TBRC, 4th Floor

Contact Information

Education

PhD, University of Calcutta, Indian Statistical Institute, India

Biography

I am a researcher with over 15 years of experience in precision medicine, focusing on identifying genomic and epigenomic modifications in prostate cancer that contribute to metastasis and therapy resistance. My work involves developing novel algorithms and performing genomics and functional analysis to identify clinically relevant markers for diagnostics and precision therapy development. I have contributed to several landmark and practice-changing research studies (NEJM 2016, Nature Medicine 2016, PNAS 2019, Nature Communication 2021, Cancer Discovery 2023). As the leader of my research group, I envision collaborating closely with clinicians and translational scientists to pursue a multidisciplinary approach to my research, resulting in productive research publications and clinical trials.

During my training, I became an expert in large-scale cancer genome and epigenome analysis, both in wet lab assays and bioinformatics. My training includes graduate studies at the Indian Statistical Institute and a postdoctoral fellowship with Dr. Peter S. Nelson, a leader in prostate cancer genomics. My expertise includes analyzing tumor genomes, studying functionally relevant mutations, and developing machine learning frameworks for predicting homologous recombination deficiency.

Honors and Awards

PCF Young Investigator Award, 2019

Research Interests

As the Principal Investigator of a research group at the Medical College of Wisconsin, I am committed to advancing precision medicine tools for prostate and other cancer types. My research focuses on several key areas:

  1. Developing tools for precision medicine
  2. Advancing liquid biopsy approaches
  3. Exosome and cell-free DNA
  4. Refining molecular subtypes of prostate cancers via multi-omics analysis
  5. Preclinical testing of novel therapeutic approaches

I serve on the editorial board for Translational Oncology and as Associate Editor for the Genitourinary Oncology edition of Frontiers journals, focusing on disseminating discoveries about DNA repair pathways in cancer. My work has focused on developing precision medicine tools that have made, or have the potential to cause significant impacts in the fields of precision medicine and therapeutics.

A significant focus of my research is the study of circulating tumor DNA (ctDNA) from liquid biopsies in patients with metastatic prostate cancer. My work in this area has led to the development of novel computational tools and a targeted sequencing panel optimized for ctDNA assays. In a 2023 study published in Cancer Discovery, we demonstrated that nucleosome patterns in ctDNA can reveal transcriptional regulation of advanced prostate cancer phenotypes. By sequencing plasma ctDNA whole genomes from patient-derived xenografts, we identified nucleosome positioning patterns associated with transcriptional activity at regions of genes, promoters, histone modifications, transcription factor binding, and accessible chromatin. This study highlighted the activity of key phenotype-defining transcriptional regulators, such as AR, ASCL1, HOXB13, HNF4G, and GATA2. To distinguish neuroendocrine prostate cancer (NEPC) and androgen receptor active prostate cancer (ARPC) in patient plasma samples, we developed prediction models that achieved accuracies of 97% for dominant phenotypes and 87% for mixed clinical phenotypes. This approach provides diagnostic advantages for precision oncology, demonstrating that ctDNA can offer comparable results to traditional methods like immunohistochemistry or transcriptome profiling from tumor biopsies.

My other interest areas include developing therapeutic strategies to overcome treatment resistance in advanced prostate cancers, particularly through novel approaches to DNA-damaging agents. I am dedicated to developing biomarkers for DNA-damaging agent sensitivity and expanding the scope of various DNA-damaging therapies, such as radiation, PARP inhibitors, and radionuclide therapies. Additionally, I am pioneering methods to assess tumor genomic and epigenomic aberrations using circulating tumor DNA.

Research Experience

  • Developed tools to analyze ctDNA for detection of phenotypic subtypes of prostate cancers
  • Developed tools for functional DNA repair deficiencies
  • landscape discovery: Germline DNA repair contribution in metastatic prostate cancer
  • Discovery of novel molecular subtype of prostate cancers

Clinical Expertise

Molecular tumor board: basic biology and bioinformatics coordinator

Methodologies and Techniques

  1. Developing novel molecular assay protocol development
  2. Large-scale Genomics (Cancer genomics: Germline and somatic)
  3. Multi-omics analysis (DNA, RNA, CUT&TAG, fragmentomics)
  4. Preclinical testing of novel biomarkers for clinical translation
  5. Clinical genomics analysis
  6. Bioinformatics pipelines
  7. Advanced methods for computational biology

Publications