March 2020
MESSAGE FROM DR. RAMON PARSONS
During this challenging time of the COVIC-19 pandemic, I want to thank you—the Tisch Cancer Institute community—for your dedication to our mission and your vigilance in the face of uncertainty. While heeding important guidelines to ensure the safety of all, you continue to provide care and support to cancer patients and conduct the basic and translational research that makes a difference in their lives. Whether working on site or remotely, everyone is contributing to the excellence that is our norm.

As you will read in this issue, we have much to celebrate, including newly awarded grant funding, new industry collaborations, new publications, and a new dataset platform. Additional grant awards are about to be finalized, and we are on a solid trajectory toward renewed funding for our Cancer Center Support Grant from the National Cancer Institute. These accomplishments are a tribute to the entire TCI community. I am very grateful and I thank you.
Cancer Clinical Trials Update

With the rapidly changing landscape in clinical care as a result of the COVID-19 pandemic and the need to ensure the safety of our patients, staff, and faculty, the Icahn School of Medicine at Mount Sinai has issued guidance statements for clinical research. For oncology-related research, we have developed additional recommendations regarding clinical research policies in order to continue life-saving therapies for our cancer patients while complying with CDC and Mount Sinai Hospital policies related to COVID-19.

Associate Director of Clinical Research, The Tisch Cancer Institute
  • Proposal Submission & Award Management
  • Human Subjects & Clinical Trials
  • Animal Welfare
  • Peer Review
Cardinale Smith, MD, PhD , Chief Quality Officer for Cancer, discusses what cancer patients need to know about COVID-19.
HONORS AND GRANT AWARDS
Lectureship Award Named After Dr. Fred Hirsch
The  International Association for the Study of Lung Cancer  (IASLC) is naming its Translational Research Lectureship Award after longtime member and former IASLC CEO,  Fred Hirsch, MD, PhD . The recipient of the  Fred R. Hirsch Lectureship Award for Translational Research  will be announced at the IASLC 2020 World Conference on Lung Cancer in Singapore, August 9-12, 2020.

R01 Award - ATRX alterations
Emily Bernstein, PhD , received R01 funding from the National Cancer Institute for research on mechanisms and modeling of neuroblastoma-associated ATRX alterations . The studies will reveal the role of ATRX alterations in epigenomic reorganization, gene expression programs, protein interactions, and epigenetic inhibitor sensitivities of this aggressive neuroblastoma subtype.
R01 Award - Genetics of ocular melanoma
Anne Bowcock, PhD , received R01 funding from the National Cancer Institute for “The genetics of ocular melanoma.” Uveal melanoma (UM) is a devastating eye cancer—the second most common form of melanoma and the most common primary cancer of the eye—that is untreatable once it metastasizes. Dr. Bowcock and colleagues have identified major genetic alterations leading to UM. They will now use long read single molecule sequencing to expand findings and a fly model to identify novel therapeutic candidates. Emily Bernstein, PhD and Cathie Pfleger, PhD, are co-investigators.
Louis Sklarow Memorial Fund
David Dominguez-Sola, MD, PhD , received a grant award from the Louis Sklarow Memorial Fund for “MYC missense mutations confer self-sufficiency in growth signals during lymphomagenesis.” This study will use preclinical models of Burkitt lymphoma to decipher the mechanisms of B cell lymphoma pathogenesis and help identify strategies for targeting the P13K/AKT/mTOR pathway as a therapeutic approach.
V - Foundation
Matthew Galsky, MD , received a translational grant from the V Foundation for “Chemotherapy plus PD-1 blockade as bladder-sparing treatment for muscle-invasive bladder cancer.” The goal of the study is to be able to select patients who can have their bladder cancer cured with the combination of chemotherapy and immunotherapy without requiring surgical removal of their bladder. 
Jun Zhu, PhD , is co-PI.
2020 Exceptional Project Grants from Breast Cancer Alliance
“Targeting SHP2 as a converging node of targeted and immune therapy in triple negative breast cancer” 
“Alterations in microtubule
dynamics: the Yin and Yang of
chemoresistance in triple negative
breast cancers”
POSTDOCTORAL AND STUDENT AWARDS
Cansu Cimen Bozkus, PhD , received a Parker Institute for Cancer Immunotherapy Award as a Parker Bridge Scholar. Dr. Bozkus conducts research on using immune responses against tumor specific antigens to develop new therapies. She is a post-doctoral fellow in the laboratory of Nina Bhardwaj, MD, PhD .
Dan Filipescu, PhD , in Dr. Emily Bernstein’s lab, received a grant for research on skin cancer and melanoma from the American Skin Association . He is investigating MacroH2A as a novel chromatin regulator of the melanoma microenvironment.
Two graduate students—both PhD candidates in Cancer Biology—in Dr. Ramon Parson’s lab received Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31) funding:
Kaitlyn Bosch , for “The study of the interfacial catalysis and therapeutic potential of PTEN-L”
Abigail Lubin , for “The role of PTEN in DNA metabolism and replication”
NEW TCI SHARED RESOURCE
The Clinical Annotation Project (CAP) Cancer Dataset is available through the Office of Chief Research Informatics Officer (CRIO) to the TCI research community. CAP contains longitudinal patient data from lung cancer, prostate cancer, and multiple myeloma cases in the Mount Sinai Health System. Requests can be placed via OSTicket .

For questions, contact Dr. Daniel Robins, MD, with the Biomedical Data Science and Informatics Services at daniel.robins@mountsinai.org or 646-656-0568.
2020 SPECIALTY REPORT ON CANCER
In the specialty report:
  • Novel In Situ Cancer Vaccine
  • New Multiple Myeloma Drug
  • Optimal Dosing for Head and Neck Cancer
  • Therapies That Control Myeloproliferative Neoplasms
  • Genetic Barcoding Technology
  • Close-Up View of Immune Therapies
  • Elusive RAS Oncogene
  • Therapies for Liver Cancer

PUBLICATIONS
Restraining lysosomal activity preserves hematopoietic
stem cell quiescence and potency

 
Dr. Ghaffari and colleagues report on their studies that revealed lysosomal regulation as a new unanticipated mode of control of hematopoietic stem cell (HSC) quiescence/cycling and potency. Findings show that repressing lysosomal activity enhances HSC quiescence and potency and may inform HSC-based therapies including bone marrow transplantation.

Related preview in Cell Stem Cell
Monitoring spatiotemporal changes in chaperone-mediated
autophagy in vivo

 
This study describes a new mouse model to visualize in vivo at single cell resolution the activation of a selective route of protein degradation named Chaperone-mediated autophagy (CMA). This pathway plays a crucial role in many diseases including cancer. This new mouse model will facilitate the study of CMA during tumor progression and metastasis.
Expansion and preservation of the functional activity of adult hematopoietic stem cells cultured ex vivo with a histone
deacetylase inhibitor


This study shows that the transplantation of ex vivo valproic acid (VPA) treated adult mobilized peripheral blood and bone marrow hematopoietic stem cells (HSCs) into immune‐deficient mice led to nonbiased long‐term multilineage hematopoietic cell engraftment including T cells. These data support the use of VPA‐mediated ex vivo HSC expansion for future gene modification strategies.
Light-induced control of protein destruction by opto-PROTAC


PRoteolysis TArgeting Chimera (PROTAC) has recently emerged as one of the hottest strategies in drug discovery. However, PROTACs may potentially lead to uncontrolled protein degradation, which could result in systemic toxicity. This paper reports on the development of opto-PROTACs that enable the degradation of protein targets in a spatiotemporal manner by adding a photolabile caging group to PROTACs. This enables a generalized platform for the development of light-controlled PROTACs as a precision-medicine approach for treating cancer and other diseases.
Cell death through the ages: The ICDS 25th Anniversary Meeting
From the laboratory of Jerry Chipuk . Authors include Jarvier N. Mohammed, BS; Jesse D. Gelles, PhD; Camila Rubio- Patiño , PhD; Madhavika N. Serasinghe, PhD; Andrew P. Trotta, PhD


In June 2019, the International Cell Death Society (ICDS) held its 25th anniversary meeting at the Icahn School of Medicine at Mount Sinai. This report provides a summary of the meeting and highlights trending research in the fields of cell death, autophagy, and immunology, and their impact on health and disease.
INDUSTRY COLLOBORATIONS
Mount Sinai Health System and Harbour BioMed (HBM) have entered into a collaboration to advance novel biotherapies for the treatment of cancer and coronavirus COVID-19. “We are pleased to be able to collaborate with HBM at this time and leverage our experience in therapeutic antibody generation as well as the viral expertise of the Microbiology Department with the unique human antibody producing mice from Harbour,” said Thomas Moran, PhD , Professor of Microbiology and Immunology, and Director of the Center for Therapeutic Antibody Development.

Tacitus Therapeutics —a clinical-stage biotechnology company—has launched in collaboration with the Mount Sinai Health System to develop stem cell therapies initially targeting blood cancers and related clotting disorders . Their first therapy, HSC100, currently is being investigated in a Phase I clinical trial . Ronald Hoffman, MD , and Camelia Iancu-Rubin, PhD , are scientific co-founders of Tacitus Therapeutics.
EVENTS

Marshall Posner, MD , presented two abstracts at the Multidisciplinary Head and Neck Cancers Symposium in February 2020:
 
  • De-Escalated Adjuvant Therapy after Transoral Robotic Surgery for HPV related Oropharyngeal Carcinoma: The SiRS Trial
  •  Survival and Quality of Life Analysis in a Randomized Deintensification Trial for Locally Advanced HPV Positive Oropharynx Cancer Patients
 
The trials—part of a coordinated effort to reduce radiation therapy dose for patients with HPV positive oropharyngeal carcinoma—produced excellent results.
 


Please note that all TCI events are cancelled until further notice.
MOUNT SINAI CANCER IN THE NEWS - CLICK HERE
Do you have news for the next issue of  TCI Connections

Please send to  Janet Aronson and Rhaisili Rosario

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
Co-editors: Janet Aronson and Rhaisili Rosario
Past issues of    TCI Connections    are available on the TCI website.