July 2022

Proteogenomics Designation

The Office of Cancer Clinical Proteomics Research at the National Cancer Institute (NCI) has awarded $4.2 million over five years to Pei Wang, PhD, and Avi Ma’ayan, PhD, to support Mount Sinai’s Proteogenomic Data Analysis Center (PGDAC). The Center is one of four PGDAC teams comprising NCI’s Clinical Proteomic Tumor Analysis Consortium, which is dedicated to accelerating research and care for people with cancer by understanding how proteins and genes contribute to cancer. Mount Sinai’s PGDAC is focused on identifying potential biomarkers and drug targets for cancer, uncovering new insights into cancer biology, and developing bioinformatics tools for more advanced investigation and discovery from cancer-related datasets.

 

Read More from the NCI

Mount Sinai Press Release


Grant Awards

John Sfakianos, MD, is one of just two recipients of the 2022 Bladder Cancer Research Innovation Award from the Bladder Cancer Advocacy Network. Dr. Sfakianos and Co-PI Amir Horowitz, PhD, will utilize spatial transcriptomics and imaging mass cytometry in patient tumor samples before and after treatment with Bacillus Calmette-Guerin (BCG)—the most common intravesical immunotherapy for treating early-stage bladder cancer—to glean information about the role of the immune response in resistance to BCG in patients with non-muscle invasive bladder cancer.

Eirini Papapetrou, MD, PhD, was awarded RO1 funding from the National Cancer Institute for “Mechanisms and Therapeutic Implications of Human Clonal Hematopoiesis Mutations.” Clonal hematopoiesis (CH)—the presence of clonally expanded hematopoietic cells in the bone marrow and blood of healthy individuals—is recognized as a near-universal phenomenon that predisposes to myeloid malignancies and offers an opportunity to understand the initiating processes of oncogenesis. This project will harness unique genetic models developed by the Papapetrou Lab to characterize the cell-intrinsic and extrinsic effects of CH mutations and investigate the mechanisms that govern the initiation and progression of leukemogenesis.

Maria Soledad Sosa, PhD, received grant funding from Susan G. Komen for research aimed at elucidating the mechanisms of reactivation of dormant early-stage breast cancer cells once they have lodged at target sites. Dr. Sosa and team will also investigate pre-clinical strategies using small molecule inhibitors to prevent reactivation of dormant early-stage tumor cells and, consequently, extend the remission phase. The award is one of 48 new research projects that are focused on improving patient outcomes for patients with the most aggressive breast cancers.

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Saghi Ghaffari, MD, PhD, received R01 grant funding from the National Heart, Lung, and Blood Institute for “Towards Understanding Molecular Mechanisms of Human Hematopoietic Stem Cells’ Quiescence.” The goal of the project is to uncover the effects of dynamic modulations of lysosomal activity on human hematopoietic stem cell function, which is relevant to mechanisms that control the dormancy of leukemic stem cells.

Hanna Irie, MD, PhD, and collaborators at The City University of New York were awarded a pilot grant as part of the DISRUPT program, funded by the Stand Up To Cancer Health Equity Breakthrough Team Research Grant Program (Nina Bickell, MD, MPH, Leader). The goal of the project—“Injectable Hydrogel-Nanomaterial Composites for Local Delivery and Detection of Doxorubicin for the Treatment of Triple Negative Breast Cancer"—is to develop better ways to deliver cancer therapeutics to minimize toxicities that could contribute to disparities in treatment completion among Black patients with triple negative breast cancer. 

Rajwanth Veluswamy, MD, is team co-leader on a multi-institution grant from Stand Up To Cancer (SU2C) as part of SU2C’s Health Equity Initiative, which focuses on increasing diversity among patients in cancer clinical trials and improving cancer outcomes and screening rates in medically underserved communities.

 

Vamsidhar Velcheti, MD, NYU Langone Health’s Perlmutter Cancer Center, is project team leader. Balazs Halmos, MD, Montefiore Einstein Cancer Center, and Brian Henick, MD, Columbia University’s Herbert Irving Comprehensive Cancer Center, are team principals.

 

The team will use an artificial intelligence-assisted smartphone and web-based app to monitor the side effects of immunotherapy treatment in a highly diverse group of patients with non-small cell lung cancer in New York City.

 

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Jerry Chipuk, PhD, received a National Science Foundation award from the Cellular Dynamics and Function Program for “BCL-2 Family Interactions With 2-Trans-Hexadecenal Define Pro-Apoptotic And Anti-Apoptotic Classifications.” The aim of the project is to redefine the apoptotic pathway in the context of fundamental cell biology and metazoan development.

Jenna Newman, PhD, postdoctoral fellow in the Bhardwaj Lab, received a Lloyd J. Old Memorial Postdoctoral Fellowship in Tumor Immunology from the Cancer Research Institute (CRI) through the CRI Irvington Postdoctoral Fellowship Program. Jenna studies tumor-reactive T cells in B16F10 melanoma.

Michelle Alyssa Tran, MD/PhD candidate in the laboratory of Nina Bhardwaj, MD, PhD, received a Ruth L. Kirschstein NRSA for Individual Predoctoral MD/PhD Degree fellows (F30) award for “Dissecting Innate Immune Mechanisms of Resistance to Checkpoint Blockade Therapy in Bladder Cancer.”

Faculty Promotions

Congratulations to the following faculty on their promotions:


New Faculty

Alaina Kessler, MD, MPH, has joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology) with a clinical focus on breast medical oncology. Dr. Kessler earned her MD and MPH at the University of Connecticut. She completed residency in Internal Medicine and fellowship in Hematology and Medical Oncology, including serving as Chief Fellow, at the Icahn School of Medicine at Mount Sinai. Dr. Kessler will serve as Assistant Director of Oncology Quality and Safety and will see patients at the Dubin Breast Center and the Blavatnik Family Chelsea Medical Center.

TCI Cores in Development:

 Bioinformatics for Next Generation Sequencing

The Bioinformatics for Next Generation Sequencing (BiNGS) core, led by Ernesto Guccione, PhD, and Dan Hasson, PhD, provides computational analyses for cancer investigators.


The mission is to further scientific discoveries by establishing robust computational pipelines for analyzing NGS datasets and training platforms, focusing on transcriptomics and epigenomics datasets. BiNGS is available to TCI member laboratories and the wider Mount Sinai and global research communities.


BiNGS staff advise on experimental design and protocols related to NGS technologies, perform data quality evaluation and data analysis, and assist in data interpretation, hypothesis formulation, and data visualization.


Recent additions:


  • New pipelines for single cell data analysis are now available for scRNA-seq and scATAC-seq datatypes.


  • Data analysis services for scMulti-omics and Spatial Transcriptomics will be available in late 2022.


For more information, please contact Dr. Guccione, Dr. Hasson, or Jerry Edward Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.

Publications

Brianna M Jones, MD; Dillan Villavisanis; Richard Bakst, MD; Marshall Posner, MD; Eric Genden, MD; and colleagues

 

High failure rates in young nonsmoker nondrinkers with squamous cell carcinoma of the oral tongue

Laryngoscope. 2022 Jun 18. PMID: 35716359



This study compared young patients to older patients with squamous cell carcinoma of the oral tongue (SCCOT) without prior drinking or smoking history—a population that is poorly characterized in the literature. Findings show that SCCOT in young, non-drinking, non-smoking patients is a highly aggressive malignancy with high rates of locoregional recurrence and distant metastasis. Further translational studies are planned to address the biology of tongue cancer in this unique population and optimize treatment and surveillance.

Paula Restrepo; Sherry Bhalla, PhD; Alessandro Lagana, PhD; Samir Parekh, MBBS; and colleagues


Signature predicts response to selinexor in multiple myeloma

JCO Precision Oncology. 2022 Jun 6. PMID: 3570479

 

This study presents a novel, three-gene expression signature that predicts selinexor response in multiple myeloma. This signature has important clinical relevance as it could identify patients with cancer who are most likely to benefit from treatment with selinexor-based therapy, especially in earlier lines of therapy.

Jian Jin, PhD; Xufen Yu, PhD; He Chen; Ümit Kaniskan, PhD; and colleagues


TF-DUBTACs stabilize tumor suppressor transcription factors

Journal of the American Chemical Society. 2022 Jul 5. PMID: 35786952



Dr. Jin and Wenyi Wei, PhD, Harvard Medical School, led a research team that developed a new technology, called TF-DUBTAC, for stabilizing tumor suppressor transcription factors (TFs) by hijacking the cellular deubiquitination system. TF-DUBTACs, which are novel heterobifunctional molecules, provide a generalizable platform to achieve selective stabilization of tumor suppressor TFs and a new therapeutic strategy for treating cancer.

Lin Wang; David Mulholland, PhD; and colleagues


World Trade Center dust exposure promotes cancer in PTEN-deficient mouse prostates

Cancer Research Communications. 2022 Jun 27



In this study, Dr. Mulholland and team used genetically engineered mouse models with prostate-specific deletion of the PTEN tumor suppressor to study the impact of World Trade Center (WTC)-dust exposure on deposition of dust particles, inflammation, and cancer progression. Findings show that chronic inflammation, induced by WTC dust exposure, promotes more aggressive cancer in genetically predisposed prostates and potentially in patients.

Amaia Lujambio, PhD; Marina Ruiz de Galarreta, PhD; and colleagues


Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma

Nature Medicine. 2022 Jun 23. PMID 35739268

 

Multiomics analysis of tumor samples from the phase 1b GO30140 and phase 3 IMbrave150 trials reveals baseline immune and genetic features that might identify patients with advanced hepatocellular carcinoma who will benefit from atezolizumab and bevacizumab combination therapy.

Presentations

Deirdre Cohen, MD, chaired a June 29 webinar,

Institutional Perspectives in Cancer - GI


Speakers and Topics:


Augusto Villanueva, MD, PhD

HCC: First Line Therapy


Deirdre Cohen, MD

Updates in Biliary Tract Cancer: Moving Toward the Target


Celina Ang, MD

Updates in Esophageal Cancer


Peter Kozuch, MD

Emerging Evidence to Support CT DNA in the Care of Colon Cancer


The entire webinar can be viewed here.

Upcoming Presentation

Department of Medicine Grand Rounds

July 23, 8:30 am

Thomas D. Schiano, MD and Douglas Tremblay, MD

"Splanchnic Vein Thrombosis in Myeloproliferative Neoplasms: Current Concepts and the Mount Sinai Multidisciplinary Approach"

MOUNT SINAI CANCER IN THE NEWS - CLICK HERE

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.
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  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