April 2022
New Center of Excellence for Pancreatic Cancer
The Center of Excellence for Pancreatic Cancer (COE) has joined the ranks of TCI’s other centers of excellence. Under the leadership of Karyn Goodman, MD, MS; Deirdre Cohen, MD; and Daniel Labow, MD, the new COE features multidisciplinary, holistic care and novel therapeutics via clinical trials.
A unique component of the COE is the Center of Excellence for Pancreatic Cancer Multidisciplinary Team (Pancreas MDT)—a well-coordinated one-stop shop providing comprehensive diagnostics, evaluation, and a personalized treatment plan, all in one day and at one location (Mount Sinai West).
“At the end of their visits, patients walk out with an easy-to-understand-and-follow treatment plan, put together by some of the best minds for treating and researching pancreatic cancer,” said Dr. Goodman. “It can take several weeks for a patient to get a treatment plan for pancreatic cancer. We do it in one day.”
Surgeons at the COE are skilled in the latest robotic techniques, including irreversible electroporation. And, the COE is pioneering new techniques such as precise tumor targeting using real-time imaging during radiotherapy delivery and respiratory gating to minimize the impact of breathing motion during treatment, as well as multi-drug regimens that may extend survival.
Mount Sinai’s pancreatic disorders treatment program is one of the most experienced in the United States, with recognition from the National Pancreas Foundation and recent grant funding from the Canopy Cancer Collective—a network that connects expert clinicians and researchers to foster optimal cancer care and improved outcomes—to enhance and maximize our multidisciplinary treatment approach.
Prostate Screening Goes Mobile
April 1 marked the official launch of the Robert F. Smith/Mount Sinai Mobile Prostate Cancer Screening Unit. The mobile unit will bring diagnostic screening to men in Central, East and West Harlem, the Upper East Side, and Queens, who might otherwise not be screened and who are vulnerable to prostate cancer. A goal is to lower prostate cancer deaths by 25 percent among Black males in the areas immediately surrounding The Mount Sinai Hospital and Mount Sinai Queens. Initiated and led by Ash Tewari, MBBS, Chair of Urology and Director of the Center of Excellence for Prostate Cancer, the mobile unit is equipped to perform screenings and tests including the prostate-specific antigen test, digital rectal exam, ExactVu™ micro-ultrasound system, EchoNous bladder scanner, genomics testing, and more.

Faculty News
Peter Kozuch, MD, was promoted to Professor of Medicine (Hematology and Medical Oncology). Dr. Kozuch is Site Director for the Division of Hematology and Medical Oncology at Mount Sinai West, and is an Associate Program Director for the Mount Sinai Health System’s hematology and medical oncology fellowship program. 
Michal Bar-Natan, MD, was promoted to Associate Professor of Medicine (Hematology and Medical Oncology). Dr. Bar-Natan is a member of the myeloproliferative neooplasms and adult leukemia teams and leads research efforts in acute lymphocytic leukemia.
Stephanie Blank, MD, has taken on the role of President of the Society of Gynecologic Oncology, effective March 21, 2022. She most recently served as President Elect I of the professional organization, which advances the prevention, early diagnosis, and treatment of gynecologic cancers. Dr. Blank is Associate Director of Women’s Cancers for The Tisch Cancer Institute.
Joseph Sparano, MD, TCI Deputy Director and Chief of Hematology and Medical Oncology, will deliver the keynote lecture—“Optimising adjuvant treatment in HR+/HER2 negative early breast cancer”—at the European Society of Medical Oncology (ESM0) Breast Cancer Congress on May 3, 2022.
Awards and Honors
Scott Friedman, MD, was selected, through a highly competitive process, to receive the Mount Sinai Faculty Council Lifetime Achievement Award. The Awards Ceremony will be held via Zoom on May 4. Dr. Friedman is Dean for Therapeutic Discovery, Fishberg Professor of Medicine, Professor of Pharmacologic Sciences, and Chief of the Division of Liver Diseases.

The following Hematology and Medical Oncology faculty will also be presented with awards from the Committee on Special Awards, part of the Dean’s Research Council at the Icahn School of Medicine at Mount Sinai, on May 4:
  • Rajwanth Veluswamy, MD, recipient of the Dr. Harold and Golden Lamport Research Award, which recognizes junior faculty in either basic science or clinical research.
Natasha Kyprianou, PhD, is the recipient of the 2022 Richard D. Williams, MD Prostate Cancer Research Excellence Award from the Urology Care Foundation. Professor of Urology, Oncological Sciences, and Pathology, and Vice-Chair for Basic Sciences Research at the Icahn School of Medicine at Mount Sinai, Dr. Kyprianou received this Award of Distinction in recognition of her outstanding and impactful research in the field of prostate cancer over the past 10 years. Dr. Kyprianou’s work is focused on understanding the mechanisms of therapeutic cross-resistance between antiandrogens and taxane chemotherapy, which provided the scientific basis for recent clinical trials for the treatment of advanced castrate-resistant prostate cancer and hormone-sensitive prostate cancer. Dr. Kyprianou is the first woman to receive this award. It will be presented at the American Urological Association Annual Meeting on May 14.
Alice Macchia, visiting PhD student from Spain in the In Vivo Imaging of Metastasis Laboratory of Jose Javier Bravo-Cordero, PhD, received an EMBO fellowship to support her stay at Mount Sinai. EMBO—the European Molecular Biology Organization—supports talented researchers at all stages of their careers and fosters the exchange of scientific information. Dr. Macchia’s PhD thesis is focused on the characterization of the biological and molecular processes behind the progression of prostate cancer, with a focus on cell-cell and cell-microenvironment communication.
Grant Award
Jerry Edward Chipuk, PhD, has received a Melanoma Research Program Mid-Career Accelerator Award from the Department of Defense, Congressionally Directed Medical Research Programs. Dr. Chipuk’s project—“The Mitochondrial Unfolded Protein Response Impacts Melanoma from Initiation to Patient Prognosis”—is a collaborative effort between multiple TCI Shared Resource Facilities (Biostatistics, Flow Cytometry, Bioinformatics for Next Generation Sequencing, and Human Immune Monitoring Center) and Department of Oncological Sciences Research Resources (Immunohistochemistry and the Mitochondrial Analysis Facility).
TCI Shared Resource Facilities:
Microscopy Core Highlights
The Microscopy Shared Resource Facility (MSRF), Deanna L. Benson, PhD, Director, provides TCI members access to equipment, training, expert consultation, and collaborative opportunities across a full-range of light and electron microscopy applications, including confocal, multiphoton, super-resolution, in vivo imaging, light sheet, widefield, and transmission electron microscopy.

The most recent addition is a Leica Stellaris Confocal microscope, located on the sixth floor of Atran. It is fully capable of fixed and live imaging and is particularly well suited to parsing and imaging multiple fluorophores in the same sample and at high resolution.

The capabilities of the microscope systems together with the skills of the team support TCI studies that include multichannel immunofluorescence for tumor diagnostics, localization of cell signaling and growth regulatory molecules, tumor cell migration and invasion, and cell biological mechanisms of metastasis and dormancy.

The MSRF sponsors monthly seminars featuring scientists using microscopy or vendors developing relevant new technology. For example, Dr. David Unnersjö-Jess with the University of Cologne presented his work at high resolution in cleared tissue; also, a leading supplier of dynamic single-molecule and cell avidity analysis instruments, LUMICKS, presented their C-Trap optical tweezers for manipulating single molecules.
For more information, researchers can contact Dr. Benson at 212-824-8974 or Jerry Edward Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.
Health Disparities Research Consultation
The Institute for Health Equity Research (IHER), led by Carol Horowitz, MD, MPH, and  Lynne Richardson, MD, is pleased to offer a Health Disparities Research Consultation Service for Mount Sinai Investigators currently involved in or planning for health equity/disparity studies.
Directed by Nihal Mohamed, PhD, the Health Disparities Research Consultation Service provides expert advice from experienced disparities researchers whose expertise extends across multiple research disciplines, including aging, cancer prevention, health behavior, community engagement and outreach, and biomedical and translational research. Consultations are intended to encourage and enhance the conduct of health disparity science across the Mount Sinai Health System. The first two hours of consultation are free.
For more information, visit the IHER website or contact Dr. Mohamed at [email protected] or 609-651-1955.
Nature Communications. 2022 Mar 24. PMID: 35332150

Dr. Powell and colleagues report on a gene signature distinguishing invasive and non-invasive early-stage lung adenocarcinoma (esLUAD) that can be used to estimate an Invasiveness Score that is strongly associated with survival. Using a novel genomics network model, they identified aurora kinase as a master regulator of the gene signature and a therapeutic target for treatment of esLUAD.

Cell Reports. 2022 Apr 5. PMID: 35385731

ARID2 is the most frequently mutated switch/sucrose non-fermentable (SWI/SNF) gene in melanoma, whose tumor suppressive functions remain ill-defined. Dr. Bernstein and team demonstrate that upon ARID2 depletion, the PBAF complex fails to assemble, altering BAF genomic occupancy with consequences on chromatin accessibility, transcription factor binding, and transcriptional changes that promote metastasis. Their study is the first to characterize the tumor-suppressive functions of ARID2 in melanoma. Findings suggest that patients whose melanoma tumors have an ARID2 mutation may have more aggressive disease and may need to be treated differently.
Cancer Cell. 2022 Apr 6. PMID: 35390296

Dr. Parekh and team studied the humoral and cellular immune response to the COVID-19 vaccine longitudinally in a cohort of 476 multiple myeloma (MM) patients. They showed that a third dose significantly increased the level of COVID specific antibodies and T cells, as well as neutralization of COVID-19 virus in MM patients; however, these levels were below those observed in healthy individuals. Findings underscore the need for additional doses of vaccination or passive immunization, as well as continued monitoring of immune responses in individual MM patients that may remain vulnerable after third-dose vaccination.
STAR Protocols. 2022 Mar 18. PMID: 35313708
Activation techniques of BAX, a pro-apoptotic protein, are crucial to studying the intrinsic pathway of apoptosis, since thousands of pro-apoptotic signals converge on BAX activation. Current methodologies are predominantly limited to membrane permeabilization studies, which assess endpoint functionality of oligomeric BAX, but overlook early activation steps of cytosolic BAX. This study reports on FLAMBE—a fluorescence polarization assay to detect activation of recombinant BAX. Dr. Chipuk and team also describe a dual-metric parameterization strategy for distillation of kinetic data and comparative analyses when studying candidate ligands.
Emanuela Taioli, MD, PhD, and colleagues
Carcinogenesis. 2022 Mar 3. PMID: 35239955

This study demonstrates statistically significant differences in DNA methylation and gene expression in tumors of World Trade Center (WTC)-exposed prostate cancer patients compared to non-WTC prostate cancer patients. Pathway analysis revealed several candidate pathways through which WTC dust exposure may be associated with epigenetic changes, which likely increased tumorigenesis potential in prostate tissues. Identifying which genes are dysregulated could have implications for cancer screening and treatment in this high risk population.
Xufen Yu, PhD; Jian Jin, PhD; and colleagues

Nature Cell Biology. 2022 Mar. PMID: 35210568

A research team led by Greg Wang, PhD, UNC Chapel Hill, and Jian Jin, PhD, discovered that EZH2, an oncogenic histone methyltransferase, has a non-canonical function in activation of oncogenes through its hidden transactivation domain in mixed-lineage leukemia (MLL)-rearranged leukemias, which differs from the well-known canonical function of EZH2 related to gene repression via trimethylation of histone H3 lysine 27. The team developed a novel EZH2 PROTAC degrader, MS177, which effectively suppressed both canonical and non-canonical oncogenic activities of EZH2, resulting in much superior growth inhibition of MLL-rearranged leukemia cells both in vitro and in vivo to EZH2 catalytic inhibitors. This research provides support for pharmacological degradation of EZH2 as a novel and superior therapeutic strategy to pharmacological inhibition of EZH2 for the treatment of MLL-rearranged leukemias and other EZH2-dependent cancers.
Thomas Marron, MD, PhD, and colleagues

Nature Medicine. 2022 Mar 28. PMID: 35347282
This “comment” article discusses the need for smaller, shorter-duration, focused trials including extensive molecular and cellular characterizations to rapidly define mechanisms of drug response and resistance and provide a clearer understanding of how cancer immunotherapy agents modulate the immune system. This will enable biomarker identification and more effective development and use of immunotherapies. The authors propose that the optimal trial design in this window-of-opportunity setting will require five key innovations in approach: multidisciplinary teams, novel statistical methods, maximum tissue access, definition of clinically meaningful response, and adaptive clinical trial designs.
Michael Hwang, MD (former resident at Mount Sinai); Mai Takahashi, MD (PGY3); Marshall Posner, MD; and colleagues
Frontiers in Oncology. 2022 Apr.
This clinical study looked at the long-term survival and quality of life outcomes in patients on a randomized study of deescalated therapy for locally advanced HPV tumors, known as the Quarterback Trial. Findings demonstrated excellent survival and improved quality of life in patients who received a reduced dose of chemo radiotherapy after induction therapy for advanced cancers.
Book Chapter in HEAD AND NECK: "Human Papilloma Virus Associated Head and Neck Squamous Cell Carcinoma." 2022 Apr 8.
This book chapter presents a review of the treatment options for recurrent and metastatic human papillomavirus-associated oropharyngeal squamous cell carcinoma. Current options include surgery and/or radiation, systemic therapies including cytotoxic chemotherapy, molecular targeted agents, and immune checkpoint inhibitors.
Christie Nguyen, graduate student in the Bernstein Lab, successfully defended her PhD thesis on March 23. Christie’s research focus is on the role of the transcription factor REST in the context of melanoma development and metastasis. Her studies have been funded by a NIH F30Ruth L. Kirschstein Individual Predoctoral NRSA for MD/PhD and other Dual Degree Fellowships.
Upcoming Presentations and Retreat

April 21
Leslye M. Heisler Associate Professor for Lung Cancer Excellence
Penn Medicine
April 28
Jodi Fisher Horowitz Professor in Leukemia Care Excellence
Director, Cell Therapy and Transplantation
Penn Medicine

May 4

May 10
Frontiers in Oncological Sciences
MD Anderson Cancer Center

May 10
"Immunogenic Cell Stress and Death in Cancer Immunotherapy"
Guido Kroemer, MD, PhD
Institut Gustave Roussy
"Rational for Microbiota-Centered Interventions in Immune-Oncology"
Laurence Zitvogel, MD, PhD
Institut Gustave Roussy
Community Outreach and Engagement at The Tisch Cancer Institute (TCI) will hold its Spring Retreat—“Q&A with Leaders in Cancer Care”—for members of TCI and our community on Monday, May 16, 2022, 1-4 pm. The goals of the retreat are to understand the cancer burden of the community, ensure that TCI research programs work to reduce these burdens, and collaborate to disseminate evidence-based interventions and policies in the community. Topics will focus on our catchment area—the five boroughs of NYC—and catchment-relevant research. Cardinale Smith, MD, PhD, TCI’s Associate Director, Community Outreach and Engagement, will deliver the keynote address.
Questions? Email [email protected]
Do you have news for the next issue of TCI Connections

Please send to Janet Aronson (646-745-6376).

Remember to share breaking news and high impact news that might be appropriate for media coverage with Marlene Naanes (929-237-5802) in the Press Office. This may include pending FDA drug/device approvals, studies/trial results being published in high-impact journals, and patient stories. The more lead time you can give Marlene, the better—ideally, four weeks or when a paper is accepted by the journal. Embargoes will always be honored and news will only be released with your approval.
  TCI Connections  is a monthly publication of The Tisch Cancer Institute
Ramon Parsons, MD, PhD, Director
Janet Aronson , Editor
Past issues of  TCI Connections  are available on the TCI website