February 2022
Specialty Report
The 2022 Cancer Specialty Report highlights the latest discoveries and work of TCI’s investigators that advance better treatments and health.

Read the Full Report
Featured Publication
The Lancet, Gastroenterology & Hepatology. 2022 Jan 19. PMID: 35065058
This study evaluated the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma (HCC)—it is the largest study to date of perioperative PD-1-targeted monotherapy in HCC. A short course of neoadjuvant cemiplimab resulted in pathological responses in patients with resectable HCC. The findings support continued evaluation of perioperative immunotherapy to decrease recurrence rates and the development of unresectable or metastatic disease via larger clinical trials designed to validate optimal clinical endpoints that correlate with improved survival and to establish the utility and safety of pre-operative PD-1 blockade.
Faculty News
Brian Brown, PhD, was appointed Director for the Icahn Genomics Institute at the Icahn School of Medicine at Mount Sinai. He is Professor of Genetics and Genomic Sciences and Associate Director of the Precision Immunology Institute at Icahn Mount Sinai. Dr. Brown has invented new ways to target vectors and viruses to particular cell types and tissues that are being evaluated in the clinic for cancer treatments. His current research focuses on identifying the molecular and cellular factors that control tumor immunity and developing therapeutic strategies to direct the immune system to eliminate cancer.

Augusto Villanueva, MD, PhD, was promoted to Associate Professor. Dr. Villanueva’s laboratory conducts research on the development and clinical implementation of minimally-invasive biomarkers of hepatocellular carcinoma (HCC) including liquid biopsy for early HCC detection and prediction of treatment response. 
Cansu Cimen-Bozkus, PhD, was appointed to the faculty at the Icahn School of Medicine at Mount Sinai as Assistant Professor. The focus of her research, in the laboratory of Nina Bhardwaj, MD, PhD, is the characterization of antitumor T cell immunity and the immunosuppressive mechanisms that might limit the efficacy of T cell-based cancer immunotherapies in myeloproliferative neoplasms, glioblastoma and microsatellite instability-high cancers.
Shared Resource Facility Update: Flow Cytometry
The TCI Flow Cytometry Shared Resource Facility (FCSRF) provides access to state-of-the-art technologies, services, and expertise in flow cytometry to enhance scientific discovery, interaction, and productivity underlying innovative cancer research programs. The FCSRF is directed by Jordi Ochando, PhD; Christopher Bare serves as Laboratory Operations Manager.

During 2021, the FCSRF experienced substantial growth in services and staff, including:

  • Addition of the CS Cell Sorter from Cytek Biosciences. This instrument complements the Aurora analytical cytometer with a matching optical configuration allowing for up to 60 discrete fluorescent probes to be measured on each cell, as well as 6-way subpopulation purification and recovery of live cells for downstream experiments.

  • Addition of a MACSQuant® Tyto® Cell Sorter from Miltenyi Biotec for sorting of true sterile cell populations. This microfluidic cartridge-based system measures 8 probes simultaneously and recovers highly-pure live cells at high speed without the cellular stress of droplet formation.

  • Addition of a ThermoFisher Attune system, with installation expected to be completed in February 2022. This analytical system is already familiar to TCI members who have used the same model in the Dean’s CoRE.

  • Two new staff members: Laila Horta, PhD, and Guillermo Villegas, PhD. Laila performs maintenance of the Hess Center cytometers and provides expert high-dimensional data analysis. Guillermo is the Tyto expert and assists with the optimization and implementation of high stringency sorting in the microfluidic instruments.

TCI members benefit from discounted pricing.

For further information, visit the FSCSF site or contact Jerry Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.
Grant Award
Jose Javier Bravo-Cordero, PhD, received a 2022 Irma T. Hirschl/Monique Weill-Caulier Scientist Award for his cancer neuroscience research in collaboration with Deanna Benson, PhD.
Grant Opportunities
Melanoma Research Foundation
  • Career Development Awards
  • Established Investigator Awards
  • Young Investigator Research Team Award
Deadline: March 1, 2022
  • Mid-Career Bridge Grant
Deadline: April 15, 2022
For assistance, contact Lauren Walker in the Office of Development. 

Cell Reports. 2022 Jan 18. PMID: 35045282

A study from the lab of Doris Germain, PhD, in collaboration with the Guccione, Lujambio and Sia labs, reveals that mitochondrial DNA (mtDNA) of the normal liver shapes tumor progression, histology, and immune environment prior to the acquisition of oncogenic mutation. Using conplastic mice, the researchers show that mtDNA dictates the expression of the mitochondrial unfolded protein response (UPRmt) in the normal liver, and that activation of oncogenic mutations in UPRmt-positive liver increases tumor incidence and histological heterogeneity. Additionally, findings of gender disparity in the mouse model demonstrate that not only mitochondrial genetics but also sex impact liver cancer outcome—this is significant since gender disparity is observed in liver cancer in humans and remains poorly understood.
Eirini Papapetrou, MD, PhD, and colleagues
Blood Advances. 2022 Jan 18. PMID: 35042235
SF3B1K700E is the most frequent mutation in myelodysplastic syndrome (MDS), but the mechanisms by which it drives MDS pathogenesis are unclear. Based on a panel of 18 genetically matched SF3B1K700E and SF3B1WT induced pluripotent stem cell lines from patients with MDS with ring sideroblasts (MDS-RS) harboring isolated SF3B1K700E mutations, this study provides a comprehensive characterization of the transcriptional and chromatin landscape of SF3B1K700E HSPCs and nominates novel mis-spliced genes and transcriptional programs with putative roles in MDS-RS disease biology.
Christian Rolfo, MD, PhD, and colleagues

Clinical Cancer Research. 2022 Feb 10. PMID: 35144967
This manuscript, expanding prior reports with additional patients and longer follow-up, reports that entrectinib continues to demonstrate durable systemic and intracranial responses, and can address the unmet need of a central nervous system-active treatment in patients with NTRK fusion-positive solid tumors.
Darren Pan, MD; Ajai Chari, MD; and colleagues
Cancer Medicine. 2022 Jan.
PMID: 34921527

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. The combination of agents continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14).
Hematology, Transfusion and Cell Therapy. 2022 Jan 25.
PMID: 35105529

Dr. Ibrahim and Dr. Keyzner report on a patient with JAK2 mutated post-essential thrombocythemia myelofibrosis with a complex karyotype who was referred for allogeneic stem cell transplant. The patient, with a high titer donor specific anti-Human Leukocyte Antigen, was treated with the anti-CD38 monoclonal antibody daratumumab, resulting in successful desensitization and engraftment. 
Journal of Medicinal Chemistry. 2022 Feb 4. PMID: 35119851

Dr. Jin, Dr. Parsons, and team recently reported a potent, selective, and in vivo efficacious AKT degrader, MS21, which is a von Hippel-Lindau (VHL)-recruiting proteolysis targeting chimera (PROTAC) based on the AKT inhibitor AZD5363. The team now reports on structure-activity relationship studies that led to the discovery of MS21, another VHL-recruiting AKT degrader, MS143 (compound 20) with similar potency as MS21, and a novel cereblon (CRBN)-recruiting PROTAC, MS5033 (compound 35). 
Presentations and Meetings
Josep Llovet, MD, will co-chair “Advances in the Pathogenesis and Molecular Therapies of Liver Cancer,” an inaugural conference of the American Association for Cancer Research, May 5-8, 2022, in Boston. For more information and to register: AACR.org/Liver22
The Mount Sinai Liver Cancer Program hosted its sixteenth annual Liver Cancer Conference on December 17. The virtual event attracted 263 attendees, up from 150-200 attendees at previous in-person conferences. Josep Llovet, MD, PhD, served as Program Director for the conference. Amit Singal, MD, Medical Director of the Liver Tumor Program and Clinical Chief of Hepatology at the University of Texas Southwestern Medical Center, delivered the Hans Popper Lecture: Epidemiology and early detection of HCC.

Hematology and Medical Oncology Grand Rounds
Thursday, February 24, 8:30 am
Director, Thoracic Oncology Biorepository, Johns Hopkins Medicine
TCI Web Update

Information about Shared Resources Cores in Development has been added to the TCI website:

Colon Cancer Awareness and Screening
March 17, 4 pm

or Dial 1-646-876-9923; Meeting ID: 924 7666 7083
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