
Navonil De Sarkar, PhD
Assistant Professor
Locations
- TBRC, 4th Floor
Contact Information
Education
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
Research Areas of Interest
- Aged
- Animals
- Base Pair Mismatch
- Biomarkers, Tumor
- Carboplatin
- Cell Line, Tumor
- Circulating Tumor DNA
- DNA Repair
- Fanconi Anemia Complementation Group D2 Protein
- Fanconi Anemia Complementation Group N Protein
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
Research Experience
- Adenocarcinoma
- Aged
- Aged, 80 and over
- Androgens
- Animals
- Ataxia Telangiectasia Mutated Proteins
- Biomarkers, Tumor
- Cell Line, Tumor
- Cell Proliferation
- Circulating Tumor DNA
- DNA Repair
- Down-Regulation
Clinical Expertise
- Humans
Methodologies and Techniques
- Aged
- Gene Expression Regulation, Neoplastic
- Humans
- Male
- Middle Aged
- Prostatic Neoplasms
Research Interests
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.
Publications
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(Orme JJ, Taza F, De Sarkar N, Tewari AK, Arsalan Naqvi S, Riaz IB, Childs DS, Omar N, Adra N, Ashkar R, Cheng HH, Schweizer MT, Sokolova AO, Agarwal N, Barata P, Sartor O, Bastos D, Smaletz O, Berchuck JE, McClure H, Taplin ME, Aggarwal R, Sternberg CN, Vlachostergios PJ, Alva AS, Mehra N, Nelson PS, Hwang J, Dehm SM, Shi Q, Fleischmann Z, Sokol ES, Elliott A, Huang H, Bryce A, Marshall CH, Antonarakis ES.) Eur Urol Oncol. 2024 Aug;7(4):877-887 PMID: 38072760 PMCID: PMC11162506 SCOPUS ID: 2-s2.0-85199223175 12/11/2023
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(Ajkunic A, Sayar E, Roudier MP, Patel RA, Coleman IM, De Sarkar N, Hanratty B, Adil M, Zhao J, Zaidi S, True LD, Sperger JM, Cheng HH, Yu EY, Montgomery RB, Hawley JE, Ha G, Persse T, Galipeau P, Lee JK, Harmon SA, Corey E, Lang JM, Sawyers CL, Morrissey C, Schweizer MT, Gulati R, Nelson PS, Haffner MC.) NPJ Precis Oncol. 2024 May 17;8(1):104 PMID: 38760413 PMCID: PMC11101486 SCOPUS ID: 2-s2.0-85193504859 05/18/2024
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(Obasi J, Sharma K, De Sarkar N, Antonarakis ES, Kilari D.) Clinical Genitourinary Cancer. December 2024;22(6) SCOPUS ID: 2-s2.0-85203009546 12/01/2024
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Integrating PARP Inhibitors in mCRPC Therapy: Current Strategies and Emerging Trends.
(Thapa B, De Sarkar N, Giri S, Sharma K, Kim M, Kilari D.) Cancer Manag Res. 2024;16:1267-1283 PMID: 39308935 PMCID: PMC11416116 SCOPUS ID: 2-s2.0-85204934732 09/23/2024
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(Zhang A, Lau NA, Wong A, Brown LG, Coleman IM, De Sarkar N, Li D, DeLucia DC, Labrecque MP, Nguyen HM, Conner JL, Dumpit RF, True LD, Lin DW, Corey E, Alumkal JJ, Nelson PS, Morrissey C, Lee JK.) Cancer Res Commun. 2023 Nov 20;3(11):2358-2374 PMID: 37823778 PMCID: PMC10658857 SCOPUS ID: 2-s2.0-85182280871 10/12/2023
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Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer.
(Schweizer MT, Gulati R, Yezefski T, Cheng HH, Mostaghel E, Haffner MC, Patel RA, De Sarkar N, Ha G, Dumpit R, Woo B, Lin A, Panlasigui P, McDonald N, Lai M, Nega K, Hammond J, Grivas P, Hsieh A, Montgomery B, Nelson PS, Yu EY.) Prostate Cancer Prostatic Dis. 2023 Mar;26(1):194-200 PMID: 36564459 PMCID: PMC10286318 SCOPUS ID: 2-s2.0-85144705758 12/24/2022
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(De Sarkar N, Patton RD, Doebley AL, Hanratty B, Adil M, Kreitzman AJ, Sarthy JF, Ko M, Brahma S, Meers MP, Janssens DH, Ang LS, Coleman IM, Bose A, Dumpit RF, Lucas JM, Nunez TA, Nguyen HM, McClure HM, Pritchard CC, Schweizer MT, Morrissey C, Choudhury AD, Baca SC, Berchuck JE, Freedman ML, Ahmad K, Haffner MC, Montgomery RB, Corey E, Henikoff S, Nelson PS, Ha G.) Cancer Discov. 2023 Mar 01;13(3):632-653 PMID: 36399432 PMCID: PMC9976992 SCOPUS ID: 2-s2.0-85146609116 11/19/2022
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(Doebley AL, Ko M, Liao H, Cruikshank AE, Santos K, Kikawa C, Hiatt JB, Patton RD, De Sarkar N, Collier KA, Hoge ACH, Chen K, Zimmer A, Weber ZT, Adil M, Reichel JB, Polak P, Adalsteinsson VA, Nelson PS, MacPherson D, Parsons HA, Stover DG, Ha G.) Nat Commun. 2023 Jan 25;14(1):403 PMID: 36697405 PMCID: PMC9877007 SCOPUS ID: 2-s2.0-85146766901 01/26/2023
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A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA.
(Doebley AL, Ko M, Liao H, Cruikshank AE, Santos K, Kikawa C, Hiatt JB, Patton RD, De Sarkar N, Collier KA, Hoge ACH, Chen K, Zimmer A, Weber ZT, Adil M, Reichel JB, Polak P, Adalsteinsson VA, Nelson PS, MacPherson D, Parsons HA, Stover DG, Ha G.) Nat Commun. 2022 Dec 03;13(1):7475 PMID: 36463275 PMCID: PMC9719521 SCOPUS ID: 2-s2.0-85143230318 12/04/2022
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(Coleman IM, DeSarkar N, Morrissey C, Xin L, Roudier MP, Sayar E, Li D, Corey E, Haffner MC, Nelson PS.) Clin Cancer Res. 2022 Jul 15;28(14):3127-3140 PMID: 35552660 PMCID: PMC9365375 05/14/2022
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Genomic attributes of homology-directed DNA repair deficiency in metastatic prostate cancer.
(De Sarkar N, Dasgupta S, Chatterjee P, Coleman I, Ha G, Ang LS, Kohlbrenner EA, Frank SB, Nunez TA, Salipante SJ, Corey E, Morrissey C, Van Allen E, Schweizer MT, Haffner MC, Patel R, Hanratty B, Lucas JM, Dumpit RF, Pritchard CC, Montgomery RB, Nelson PS.) JCI Insight. 2021 Dec 08;6(23) PMID: 34877933 PMCID: PMC8675196 SCOPUS ID: 2-s2.0-85120888453 12/09/2021
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(Sokolova AO, Marshall CH, Lozano R, Gulati R, Ledet EM, De Sarkar N, Grivas P, Higano CS, Montgomery B, Nelson PS, Olmos D, Sokolov V, Schweizer MT, Yezefski TA, Yu EY, Paller CJ, Sartor O, Castro E, Antonarakis ES, Cheng HH.) Prostate. 2021 Dec;81(16):1382-1389 PMID: 34516663 PMCID: PMC8563438 SCOPUS ID: 2-s2.0-85114718067 09/14/2021