About

Ronny Drapkin, MD, PhD, is the Franklin Payne Professor of Pathology in Obstetrics & Gynecology at the University of Pennsylvania. He serves as the Director of Gynecologic Cancer Research at the Basser Center for BRCA and the Penn Ovarian Cancer Research Center. Additionally, he is Co-Director of the SPORE in Ovarian Cancer at Penn-Hopkins and the Translational Center of Excellence at the Abramson Cancer Center. His research investigates the origins and early evolution of gynecologic cancers, with a primary focus on high-grade serous ovarian carcinoma (HGSOC), the most lethal subtype of ovarian cancer. His work has established the Fallopian tube epithelium as the principal site of origin for HGSOC, providing a new framework for studying disease initiation, early detection, and prevention. Drapkin's lab employs an integrated, multi-scale approach, including genetically engineered mouse models, Fallopian tube–derived cell systems, and patient-derived xenografts, coupled with genomic, spatial, and single-cell profiling technologies. His current efforts aim to build a comprehensive pre-cancer atlas of the Fallopian tube, identify early signaling pathways associated with immune evasion, and understand how the tumor microenvironment contributes to disease progression. His goal is to translate these insights into clinically actionable strategies for early detection, risk stratification, and therapeutic intervention. Drapkin is committed to training the next generation of investigators through mentorship, fostering an environment of intellectual independence and team science.

Research topics

• Biology
• Genetics
• Computational biology
• Evolutionary biology
• Virology
• Mathematics
• Statistics
• Cancer research

Selected publications

• Tumor‐Infiltrating Nociceptor Neurons in Ovarian Cancer Treatment Resistance

  Advanced Biology · 2026-03-01

  articleOpen access

  Patients with densely innervated tumors suffer with poor outcomes, thus identifying them could define a cohort that could benefit from aggressive treatments. Most cases and deaths from ovarian cancer are associated with high-grade serous ovarian carcinoma (HGSOC). We immunohistochemically analyzed the histological subtypes of ovarian cancer (high-grade serous, low-grade serous, clear cell, mucinous, and endometrioid) for nerves; only HGSOCs were densely innervated. We previously defined that tumor-released small extracellular vesicles (sEVs) recruit nerves to the tumor bed and thus tested whether the difference in nerve infiltration amongst ovarian cancers was associated with sEVs. Using an in vitro neurite outgrowth assay, we found that HGSOC sEVs harbored robust neurite outgrowth activity. Importantly, sEVs from fallopian tube cell lines (the primary cell of origin of HGSOC) predominantly lacked this activity. Implantation of a syngeneic mouse model of HGSOC into transgenic mice lacking tumor-infiltrating nerves slowed tumor growth, sensitized disease to carboplatin, and improved survival. Consistent with this, we show that recurrent, treatment-resistant disease in patients is significantly more innervated than its matched naïve (untreated) malignancy. Taken together, these data identify dense nerve infiltration of HGSOCs and show that innervation contributes to treatment resistance.

  PublisherDOI

• Reconstruction of epithelial transcriptional trajectories reveals heterogeneous progression and early therapy-resistance programs in high-grade serous carcinoma precursors

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-09

  articleOpen access

  Abstract Background Serous-tubal intraepithelial-carcinoma (STIC) is considered the principal precursor of tubo-ovarian high-grade serous-carcinoma (HGSC), yet its biological uniformity, progression risk and potential response to poly(ADP-ribose) polymerase-inhibitors (PARPi) remain poorly defined. Methods We performed trajectory-based transcriptomic reconstruction of Fallopian-tube epithelial regions spanning normal epithelium, precursor lesions, STIC, and invasive carcinoma using pseudotime inference and publicly available spatial transcriptomic data. Gene expression and pathway dynamics were defined along pseudotime, and interpatient heterogeneity examined at both lesion and patient levels. Transcriptional signatures associated with PARPi-resistance were quantified across STICs, BRCA -mutant and BRCA -wild type subtypes. Results Trajectory inference captured a continuous transcriptional progression from normal epithelium to HGSC, with STICs occupying heterogeneous evolutionary positions rather than a single precursor state. Incidental isolated STICs(STICi) spanned early to later pseudotime states and frequently aligned with loss-of-cilium organisation and less advanced epithelial phenotypes. STICs associated with concurrent cancer(STICc) exhibited more advanced malignant progression signatures, including cell-cycle activation, epithelial-to-mesenchymal transition (EMT), interferon signaling, and DNA-repair. Histologically similar lesions occupied divergent pseudotime positions with marked interpatient heterogeneity. PARPi resistance–associated signatures were variably enriched across precursor and precancer-stage lesions, with persistence into invasive disease. Conclusions STICs are heterogeneous and occupy distinct evolutionary positions along a continuum, highlighting potentially different progression risks from normal epithelium to HGSC. STICi differ from STICc which harbour signatures of more advanced malignant progression. Heterogeneity in PARPi resistance–associated programs in STICs cautions against uniform (non-stratified) use of PARPi-based primary prevention strategies. Future research should explore evolutionary-trajectory informed biomarkers for risk stratification and early interception strategies. Translational relevance Serous tubal intraepithelial-carcinoma (STIC) represents a precursor of tubo-ovarian high-grade serous carcinoma (HGSC), offering unique translational opportunities for early detection, risk stratification, and prevention. However, its phenotypic uniformity, progression risk and therapeutic drug response are not fully understood. Our study shows that STICs are not a uniform precursor state, but instead occupy a range of evolutionary positions along a continuum from normal epithelium to invasive HGSC. This heterogeneity reflects continuous transcriptional variation rather than discrete precursor categories. We report gene expression dynamics and molecular signature changes across the malignant transformation timeline. We further illustrate that precursor lesions exhibit phenotypic variability that impacts therapeutic drug resistance-associated programs. Our data highlight potential disease biomarkers defined by evolutionary trajectory inference and transcriptional processes associated with drug resistance operating in precursor lesions. These findings may help improve our ability to distinguish clinically significant lesions and inform targeted interception strategies.

  PublisherOA PDFDOI

• Abstract 3064: Synergistic combinations of novel small molecule CtBP inhibitors with DR5 agonists or BH3-mimetic PROTACs targeting chemoresistant high grade serous ovarian carcinoma

  Cancer Research · 2026-04-03

  article

  Abstract Background: High Grade Serous Ovarian Carcinoma (HGSOC) is especially lethal due to frequent diagnosis at advanced stage and development of chemoresistance. The oncogenic transcription factors C-terminal binding proteins 1 and 2 (CtBP1/2; or “CtBP”) are transcriptional scaffolds/coregulators that drive tumor progression and metastasis in many solid tumors and are amplified in ∼10% of HGSOC, with their frequent protein overexpression correlated with poor prognosis. Results: We have previously reported that CtBP transcriptionally represses the proapoptotic Death Receptors (DR) 4/5 in HGSOC cells, preventing activation of caspase 8-dependent apoptosis. Aside from its role as an oncogenic dependency in HGSOC, CtBP is a therapeutic target encoding an NAD-dependent dehydrogenase domain against which we have developed small molecule CtBP inhibitors (CtBPi) which exhibit significant anti-tumor activity in various solid tumor models without toxicity. Our current lead CtBPi’s, NAS-2-133/134, which are naphthyl derivatives of the 1st generation CtBP inhibitor scaffold 2-hydroxyimino-3-phenylpropanoic acid, exhibit IC50 values of 4-17 µM in multiple HGSOC cell lines, while A2780 cells with homozygous deletion of CtBP1/2 (A2780/DKO) were resistant to NAS-2-134 relative to parental A2780 cells (IC50s = >>25 µM [beyond titration] vs. 20 µM, respectively), demonstrating that NAS-2-134 exhibits potent on target cytotoxic selectivity. In addition, NAS-2-134 induced caspase-8 dependent apoptosis in HGSOC cells via upregulation of DR5 and exhibited synergistic cytotoxicity when combined with the DR5 agonists MD5.1 or Biomyifi using Bliss methodology (Bliss synergy scores: MD5.1=15.8, BIOYMIFI=15.3). Further mechanistic studies revealed NAS-2-134 decreased Bcl-2 levels, which prompted evaluation of potential synergy of NAS-2-134 with BH3-mimetics venetoclax (ABT-199) and navitoclax (ABT-263), which target Bcl-2 and Bcl-2/XL, respectively. Though NAS-2-134 and ABT-199 did not exhibit synergistic cell killing in HGSOC cells, NAS-2-134 and ABT-263 exhibited strong synergy with a Bliss score of 47. Importantly, both NAS-2-134 and the closely related CtBPi NAS-2-133 demonstrated potent in vivo antitumor activity, abrogating growth of OVCAR3 xenografts in immune deficient mice. Conclusion: We demonstrate that NAS-2-134 exhibits target selective cytotoxicity in HGSOC cells via induction of caspase-8/DR5 dependent apoptosis in vitro and both NAS-2-134 and NAS-2-133 exhibit potent anti-HGSOC tumor activity in vivo; and 2) concerted targeting of CtBP and DR5 or Bcl-2/XL is synergistically cytotoxic in HGSOC cells and this strategy may lead to a future low toxicity precision therapy for chemoresistant HGSOC. Citation Format: Kranthi Kumar Chougoni, Nicholette St. Martin, Diana T. Dcona, Nari Kim, Boxiao Ding, Ronny I. Drapkin, Keith C. Ellis, Steven R. Grossman. Synergistic combinations of novel small molecule CtBP inhibitors with DR5 agonists or BH3-mimetic PROTACs targeting chemoresistant high grade serous ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3064.

  PublisherDOI

• Cycling molecular assemblies for Golgi imaging and disruption

  Nature Communications · 2026-01-28

  articleOpen access

  The Golgi apparatus is a central hub for protein trafficking and signaling, yet its rapid imaging and cell-selective disruption remain challenging. Here, we report cycling molecular assemblies (CyMA) for fast Golgi imaging and cell-selective interference. CyMA precursors are acetylated amphiphilic thiopeptides that traverse plasma membrane and are deacetylated by intracellular thioesterases. This exposes thiols that undergo palmitoylation by Golgi-resident palmitoyl acyltransferases utilizing palmitoyl-CoA. The resulting palmitoylated peptides self-assemble into dynamic nanostructures (i.e., CyMA) localized at the Golgi. Their continuous, reversible S-acylation enables near-instantaneous Golgi imaging. Replacing fluorophore with a biphenyl motif promotes CyMA accumulation and disrupts functions such as protein modifications, trafficking, and secretion, leading to cell death. This study establishes dynamic supramolecular assembly as an active and selective strategy for Golgi-targeting, pleiotropically interfering with Golgi functions, which may be applicable to targeting other organelles by utilizing alternative enzyme switches to enable kinetic trapping.

  PublisherDOI

• Rethinking ovarian cancer III: the past decade and future directions

  Nature reviews. Cancer · 2026-04-13

  article
  PublisherDOI

• Combination ATR and PARP Inhibitor (CAPRI) trial in recurrent platinum-sensitive high-grade serous ovarian cancer demonstrates activity independent of homologous recombination repair status

  Gynecologic Oncology · 2026-04-23

  article
  PublisherDOI

• 1071 HLA-E Expression in Ovarian and Endometrial Carcinomas

  Laboratory Investigation · 2026-03-01

  articleSenior author
  PublisherDOI

• Environmental justice indicators and endometrial cancer incidence: Associations with water quality, walkability and tumor molecular profiles

  Gynecologic Oncology · 2026-04-23

  article
  PublisherDOI

• Abstract 7640: Ciliated cells drive critical STING-mediated tumor suppression in fallopian tube epithelium

  Cancer Research · 2026-04-03

  article

  Abstract Mitigating DNA damage in the fallopian tube epithelium (FTE) is essential for preventing tubo-ovarian high-grade serous carcinoma (HGSC). Here we demonstrate that STING is abundantly expressed in the ciliated cells of the FTE and functions as a critical immune-independent tumor suppressor. Using patient samples, mouse models, and organoid systems, we demonstrate that ciliated cells mount a dual protective response to ovulation-associated genotoxic stress: intrinsic STING-driven apoptosis and extrinsic clearance of neighboring damaged secretory cells via TNFα secretion. This surveillance mechanism markedly limits DNA damage accumulation within the epithelial microenvironment. Crucially, while these mechanisms are vital for maintaining homeostasis and reducing genomic instability, they fail to impact p53-deficient precursor lesions as both intrinsic and extrinsic pro-apoptotic processes rely on functional p53 signaling. This study uncovers a previously unrecognized, immune-independent role for STING-high ciliated fallopian tube cells as active guardians of genomic integrity, whose loss creates a permissive niche for HGSC initiation. CONFLICT OF INTEREST STATEMENT: R.D. serves on the scientific advisory board of VOC Health and Repare Therapeutics. DGH is a previous founder and Chief Medical Officer of Imagia Canexia Health. The other authors declare that they have no competing interests. Citation Format: Jose Colina, Maria Sol Recouvreux, Alex Sobeck, Benjamin K. Johnson, Yinzhi Lin, Sreeja C. Sekhar, Rita A. Avelar, Gabriela Rivera, Yali Zhai, amber fatima, Paula DiBenedetto, Justin Baldassarre, Grace McIntyre, Jessica Teitel, Michele Cusato, Harini Ram, Noah Puleo, Karan Bedi, Jane Miglo, Hui Shen, Dafydd G. Thomas, Jutta Huvila, Dawn R. Cochrane, Ronny I. Drapkin, Yu Lei, Joanna E. Burdette, David G. Huntsman, Kathleen Cho, Sandra Orsulic, Analisa DiFeo. Ciliated cells drive critical STING-mediated tumor suppression in fallopian tube epithelium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7640.

  PublisherDOI

• Abstract 3533: Integrative spatial profiling of protein and chromosomal alterations across normal, precancer, and cancer revealed the presence of aneuploidy in the normal fallopian tube

  Cancer Research · 2026-04-03

  article

  Abstract Introduction: Simultaneous measurement of protein expression and chromosomal alterations within the same FFPE section enables direct analysis of clonal selection and disease progression from normal epithelium through precancerous to cancerous states. We developed a unified workflow based on the one-shot Orion multiplexed imaging platform (Lin et al., Nature Cancer 2023) that integrates high-dimensional protein imaging with a conventional DNA-FISH assay for in situ detection of chromosomal copy number alterations (CNAs). Traditional DNA-FISH, although widely used in diagnostic practice, requires protease digestion and permeabilization steps that destroy antigen epitopes and distort nuclear morphology, preventing reliable protein detection and limiting integration with immunofluorescence. The challenge spans both normal precursor and malignant tissues, where densely packed or overlapping nuclei complicate single-cell CNA scoring - an issue that is now particularly relevant, given the growing recognition that aneuploidy can arise even in morphologically normal epithelia. Method: Recent advances in multiplexed imaging now enable phenotypic characterization of individual cells harboring CNAs, a capability previously unattainable with conventional immunofluorescence. To realize this potential, we optimized fixation, hybridization, and imaging parameters to preserve both antigenicity and nuclear architecture while maintaining robust CNA detection. The resulting ORION-FISH workflow enables simultaneous visualization and quantification of protein states and chromosomal alterations within the same section. Results: We have found that normal fallopian tube epithelium harbors MYC and/or CCNE1, both of which are common CNAs in High Grade Serous Ovarian Cancer (HGSOC) and its precursor lesion, Serous Tubal Intraepithelial Carcinoma (STIC). We have also found that these aneuploid cells may have been under strong negative selection pressure, partially due to strong immune surveillance. Currently, we are analyzing in depth precursor samples and HGSOC specimens that will be presented at the meeting. Conclusion: We applied ORION-FISH approach to HGSOC and its precursors to generate spatial maps of aneuploidy and cell states across the normal-precancer-cancer continuum, establishing a foundation for our studies in the HGSOC Pre-Cancer Atlas 2.0. Citation Format: Tanjina Kader, Yu-An Chen, Clemens Hug, Jia-Ren Lin, Jeremy Muhlich, Euihye Jung, Charles Drescher, Ronny I. Drapkin, Peter Karl Sorger, Sandro Santagata. Integrative spatial profiling of protein and chromosomal alterations across normal, precancer, and cancer revealed the presence of aneuploidy in the normal fallopian tube [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3533.

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Recent grants

• NIH Grant K08CA108748

  NIH · $680k · 2010

• Proteomic, Genomic, and Longitudinal Pathways to Ovarian Cancer Biomarker Discovery

  NIH · $8.9M · 2021–2026

• Elafin as a biomarker in serous ovarian cancers and basal-like breast tumors

  NIH · $406k · 2013–2015

• Project 3: Investigating new treatment approaches based on DNA repair vulnerability in ARID1A mutated type I ovarian cancer

  NIH · $31.7M · 2018–2029

Frequent coauthors

• Ursula A. Matulonis

  326 shared

• Joyce F. Liu

  242 shared

• Kathleen H. Burns

  195 shared

• David D.L. Bowtell

  Peter MacCallum Cancer Centre

  187 shared

• Ie‐Ming Shih

  184 shared

• Michelle S. Hirsch

  Brigham and Women's Hospital

  175 shared

• Tian‐Li Wang

  170 shared

• Matthew Meyerson

  Dana-Farber Cancer Institute

  162 shared

Education

• B.A., Biochemistry

  Brandeis University

  1990

• Ph.D., Biochemistry

  Rutgers Graduate School of Biomedical Sciences

  1996

• M.D., General Medicine

  Rutgers Robert Wood Johnson Medical School

  1998

Awards & honors

• Franklin Payne Professor of Pathology in Obstetrics & Gyneco…
• Director, Gynecologic Cancer Research, Basser Center for BRC…
• Director, Penn Ovarian Cancer Research Center, University of…
• Co-Director, SPORE, Penn-Hopkins NIH P50 SPORE in Ovarian Ca…
• Co-Director, Translational Center of Excellence, Abramson Ca…