May 2025

Myvizhi Esai Selvan, PhD; Robert Klein, PhD; Zeynep Gümüş, PhD, and colleagues



Precision proteogenomics reveals pan-cancer impact of germline variants

Cell. 2025 Apr 9. PMID: 40233739

This study shows that inherited DNA changes can influence how genes are expressed and how proteins that drive cancer behavior are produced and modified in tumors. The research team leveraged the Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort with multiple cancer types to explore the impact of germline variations on cancer-relevant genes through multiple-omics layers. Using an approach called “precision peptidomics,” the team mapped 337,469 protein-coding germline variants onto peptides from patients’ mass spectrometry data, revealing how inherited differences can alter protein activity, impact gene expression and drive how tumors interact with the immune system. Findings emphasize the contribution of germline genetics to cancer heterogeneity and high-throughput precision peptidomics and may inform new possibilities for tailoring cancer care based on the patient’s underlying genetic makeup as well as the tumor itself.

Press Release

Tiphaine Martin, PhD, was a judge for the Health and Wellbeing track of the New York Business Plan Competition, held on April 24 in Troy, New York. The competition is organized by Upstate Capital Association of New York. Dr. Martin is Assistant Professor of Oncological Sciences in the Parsons Laboratory; she has expertise in computational biology, bioinformatics, and biostatistics. 

Doris Germain, PhD, was awarded R01 grant funding from the NCI for “Investigating the Efficacy of g-Tocotrienol for the Prevention of Post-partum Breast Cancer.” The Germain lab has identified a unique set of mouse models—in one model, genes expressed in the mammary gland during lactation are associated with tumor suppressor pathways and protect against breast cancer; in the other model, the opposite is observed and females in this model are prone to breast cancer. They further identified that the differential response to endoplasmic reticulum stress (ER stress) during lactation is at the origin of these different outcomes but that treatment with the ER stress mediated apoptosis tocotrienol can reverse the pro-tumorigenic lactation into an anti-tumorigenic lactation. This R01 aims to further dissect the mechanism of action and optimize dosing and scheduling with the goal of translating these findings to humans and expanding the protective effect of breastfeeding to more women. 

Germain Lab

Mount Sinai has received a grant for the fourth consecutive year from the American Cancer Society to help with the provision of transportation to/from all Mount Sinai locations for cancer patients identified by oncology social workers. This grant helps The Tisch Cancer Institute’s Community Outreach and Engagement Program ease the burden of cancer for patients and families.

The Microscopy and Advanced Bioimaging Core, Deanna Benson, PhD, Director, is pleased to provide updates on services, team members, equipment and more in the Core’s April newsletter.

New equipment includes:

Main Campus

• Bruker Ultima 2Pplus Multiphoton
• Zeiss Axio Observer with live cell capabilities
• New server for image analysis

W787 Campus

• Agilent Cytation C10 – High Content Screener
• Leica Stellaris 8 – Advanced Confocal

The services of The Tisch Cancer Institute Biostatistics Shared Resource can significantly increase the likelihood of successful grant awards. Researchers are reminded to allow a four-week lead time for grant development. The first step is to submit a request for services.

Questions can be directed to Erin Moshier, MSc, Managing Director.

Melanie W. Kier, MD, and Amy Tiersten, MD are Co-Principal Investigators on a Phase 1 trial that opened to patient enrollment in October 2024: A Single-Center, Open-Label, Single-Arm, Phase I Study with Dose Expansion Cohort of Sacituzumab Govitecan in Combination with Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer (NCT06040970).

The purpose of this study is to evaluate whether sacituzumab govitecan in combination with cisplatin will be safe and will increase the overall response rate in platinum-sensitive recurrent epithelial ovarian cancer and endometrial cancer. Sacituzumab govitecan is an antibody-drug conjugate composed of the irinotecan active metabolite SN-38 covalently linked to a humanized monoclonal antibody targeting trophoblastic cell-surface antigen-2. SN-38 has been shown in previous trials to be more potent than irinotecan, with increased therapeutic activity. Additionally, the antibody conjugation allows for improved drug delivery to tumor tissue with only moderate toxicity. The trial is available at The Blavatnik Family Chelsea Medical Center.

Elena Grossi, PhD; Christie Nguyen, MD/PhD; Emily Bernstein, PhD

The SWI/SNF PBAF complex facilitates REST occupancy at repressive chromatin

Molecular Cell. 2025 Apr 16. PMID: 40252649

Via epigenetic profiling of SWI/SNF complexes and their associated chromatin states in melanocytes and melanoma, Dr. Bernstein and team show that PBAF regions are less sensitive to ATPase inhibition than BAF sites and that a subset of the former colocalize with PRC2 and the transcription factor REST. REST relies on PBAF to bind chromatin and silence its target neuronal genes. The PBAF subunit ARID2 is frequently mutated in melanoma and correlates with a REST synaptic gene signature in melanoma patients. Findings indicate a unique role for PBAF in generating accessibility for a silencing transcription factor at repressed chromatin, with important implications for disease.

Press Release

Rui Sun, PhD; Robert Fisher, MD, PhD

Tripartite phosphorylation of SPT5 by CDK9 times pause release and tunes elongation rate of RNA polymerase II

Molecular Cell. 2025 Apr 10. PMID: 40250441

A team led by Dr. Fisher has discovered that the protein SPT5 plays an important role in ensuring accurate and efficient production of RNA. The enzyme CDK9 adds phosphates onto different parts of the SPT5 protein, turning SPT5 on and off at key stages of the RNA-making process. Two specific regions containing phosphorylation sites on the SPT5 protein, CTR1 and CTR2, have opposing functions that coordinately control pause release, elongation speed, and termination in HCT116 human colon cancer cells. Findings could have major implications for diseases like cancer, where gene expression goes awry. Better understanding of how SPT5 is regulated may provide insights for developing new drugs that fine-tune RNA production in cells. 

Press Release

Adam Kittai, MD, and colleagues

International consensus statement on diagnosis, evaluation, and research of Richter transformation: the ERIC recommendations

Blood. 2025 Apr 16. PMID: 40239121

This paper outlines recommendations made by an international group of experts, coordinated by the European Research Initiative on chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), for clinical care and research on Richter transformation—an aggressive lymphoma associated with poor outcomes that can develop in patients with CLL.

Sacha Gnjatic, PhD, and colleagues

The Society for Immunotherapy of Cancer perspective on liquid biopsy and radiomics based technologies for immuno-oncology biomarker discovery and application

Clinical Cancer Research. 2025 Apr 8. PMID: 40197626

The Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify important advances in biomarker technologies and to highlight advances in biomarker discovery using liquid biopsy and in vivo imaging technologies. The committee addresses advances in liquid biopsy technologies monitoring cells, proteins, nucleic acids, antibodies, and drugs or analytes, and radiomics technologies monitoring at the whole host-level imaging methods including immuno-PET and MRI technologies able to couple biomarker with physical location. By highlighting some of the most interesting recent examples contributed by these technologies, and providing examples improving outputs, the committee hopes to guide correlative research directions and assist in their becoming clinically useful in immuno-oncology.

Rahat Alam, BS; Anna Reva, MA; Igor Bado, PhD, and colleagues

Bone-induced HER2 promotes secondary metastasis in HR+/HER2- breast cancer

Cancer Discovery. 2025 Apr 2. PMID: 39835789

In this study, Dr. Bado and colleagues evaluate the prediction power of HER2-expressing (HER2E) circulating tumor cells (CTC) after analyzing over 13,000 CTCs from a cohort of 137 patients with metastatic breast cancer with initial HR⁺/HER2⁻ status and use preclinical models of bone metastasis (BM) to validate the role of HER2E CTCs in multiorgan metastases. Results provide insights into mechanisms of resistance that can be transmitted from one organ to another without genetic implications. The activation of autocrine signaling increases the possibilities for microenvironment-independent survival, a process that facilitates metastasis seeding and tissue colonization. HER2 is identified and characterized as a traceable marker that associates with bone-mediated secondary metastasis. Study findings may help improve diagnosis and guide therapeutic strategies in patients with HR⁺/HER2⁻ metastatic breast cancer. 

Kohei Takashima, PhD; Eirini Papapetrou, MD, PhD, and colleagues

Cell-autonomous dysregulation of interferon signaling drives clonal expansion of SRSF2-mutant MDS stem/progenitor cells

Blood. 2025 Mar 31. PMID: 40163808

Using human isogenic induced pluripotent stem cell-based models of SRSF2-mutant myelodysplastic syndromes (MDS) and primary MDS patient cells, Dr. Papapetrou and colleagues show that the SRSF2 P95L mutation downregulates basal STAT1 expression and that STAT1 downregulation dampens interferon (IFN) signaling in MDS stem/progenitor cells. The study provides a novel mechanistic link between slicing factor mutations and inflammatory dysregulation and suggests proteasome inhibition as a potential strategy to treat MDS with SRSF2 mutations.

Stephanie Tuminello, PhD, MPH; Raja Flores, MD; Emanuela Taioli, MD, PhD, and colleagues

Predicted effect of incidental pulmonary nodule findings on NSCLC mortality

Journal of Thoracic Oncology. 2025 Mar. PMID: 39542100

Identifying malignant lung nodules in imaging performed for other clinical reasons can help decrease the burden of non-small cell lung cancer, especially for patients not eligible for low-dose computed tomography and the medically vulnerable. This analysis reveals that clinical benefits, especially among patients with aggressive disease, can be considerable.

Xucheng, Huo, PhD; Joshua Brody, MD; Yizhou Dong, PhD, and colleagues

Enhancing antitumor immunity through chemotherapeutic-derived lipid nanoparticle-induced immunogenic cell death and CD40L/Flt3L mRNA-mediated dendritic cell activation

Journal of Controlled Release. 2025 Apr 2. PMID: 40185331

This study investigated the synergistic potential of immunogenic cell death, triggered by chemotherapeutic-derived lipid nanoparticles, in combination with Flt3L and CD40L mRNA delivery to enhance dendritic cell mobilization and activation, reprogram the tumor microenvironment (TME), and promote robust antitumor T cell responses. In a subcutaneous melanoma model, the approach led to significant tumor suppression and a 40 % complete response rate. The strategy holds promise for enhancing cancer immunotherapies by reprogramming the TME and inducing durable antitumor T cell immunity.

Subhamoy Chakraborty, PhD; Triparna Sen, PhD, and colleagues

Protocol to co-culture SCLC cells with human CD8⁺ T cells to measure tumor cell killing and T cell activation

STAR Protocols. 2025 Apr 14. PMID: 40232937

Dr. Sen and colleagues present a protocol to assess T cell activation and the ability of lurbinectedin to enhance anti-tumor responses using in vitro co-cultures of small-cell lung cancer (SCLC) cells and human CD8 T cells. They describe steps for cell seeding, treatment, co-culture setup, and assessing cell viability. The protocol provides a platform to study anti-tumor T cell responses and develop new SCLC therapies.

Eirini Papapetrou, MD, PhD, has numerous presentations in May:

• Biology & Therapy of Myeloid Malignancies Conference, May 14-17, Crete
• Hematopoietic Stem Cell and Myelodysplastic Syndromes (MDS) Symposium, May 21-22, MD Anderson Cancer Center
• Keynote speaker at Annual Hematology Conference, University Hospital of Alexandoupolis, May 31

Jose Javier Bravo-Cordero, PhD, presented “The Textures of the Tumor Microenvironment: An Integrated Imaging Perspective” at  Cancer Dormancy and Therapy Resistance: From Models to the Clinic, held May 5-7 in Rome. 

Tristen Park, MD, was an invited speaker at the Global Breast Cancer Conference 2025, held April 17-19 in Seoul. She presented “Surgical Controversies in Inflammatory Breast Cancer” and moderated a debate, “De-escalation of Surgery or Radiation in Early Breast Cancer.” Hosted by the Korean Breast Cancer Society, the international multidisciplinary conference—the largest in Asia with representation from more than 60 countries—promotes strategies to effectively diagnose and treat breast cancer and showcases cutting-edge clinical and translational research in breast cancer treatment.

Emily Bernstein, PhD, presented “Chromatin Remodeling in Cancer” at the Annual Meeting of the American Society for Biochemistry and Molecular Biology, held April 12-15 in Chicago.

Division of Hematology and Medical Oncology Grand Rounds

May 15, 8:30 am, Hess Seminar Room B

Gedalio and Sonia Grinberg/Nathaniel Wisch, MD, Endowed Visiting Lectureship

Alessandro M. Vannucchi, MD, Professor of Hematology, University of Florence

“From Leeches to Target Therapy in Polycythemia Vera”

TCI Seminar Series

Tuesdays at Noon

Davis Auditorium

May 13

Tobias Janowitz, MD, PhD, Cold Spring Harbor Laboratory

“Interorgan Communication in Cancer Cachexia”

Hosted by Ramon Parsons, MD, PhD

May 20

Ramesh Shivdasani, MD, PhD, Dana-Farber Cancer Center

“Stomach Epithelial Cell Differentiation: A Revisionist View”

Hosted by Guo-Cheng Yuan, PhD

May 27

Gabrielle Rizzuto, MD, PhD, Memorial Sloan Kettering Cancer Center

“Immune Tolerance Through the Lens of Pregnancy”

Hosted by Eirini Papapetrou, MD, PhD

Frontiers in Cancer Immunotherapy

June 6-17

Presented by The New York Academy of Sciences Cancer & Signaling Discussion Group

Nina Bhardwaj, MD, PhD, is a member of the Scientific Organizing Committee.

Registration