A Fruitful Collaboration
Dr. Posner, Dr. Cagan, and team developed a fly-to-bedside workflow to harness the power of Drosophila as a screening platform for customizing patient-specific treatments.
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A patient-specific Drosophila transgenic line was developed to model the five major variants associated with the patient's disease, and robotics-based screening identified a three-drug cocktail.
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Dr. Posner and Dr. Cagan have an NIH R21 grant to continue their studies in adenoid cystic carcinoma (ACC), a salivary gland cancer. They plan to sequence ACC patients, who have a chromosomal translocation involving the genes encoding the transcription factor MYB, and establish fly avatars which reflect the mutational landscape of the individual tumors. Using these fly avatars, they will study common signaling pathways in the tumors and screen multiple individual and combinations of drugs for activity in the avatars. |
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Luis Isola, MD, has been appointed as Senior Associate Dean for Clinical Affairs in the Icahn School of Medicine. Among the many responsibilities of this role, Dr. Isola will help elevate the visibility and reputation of cross-service line programs and centers of excellence. Dr. Isola is also Director of Cancer Clinical Programs, Director of the Bone Marrow and Stem Cell Transplantation Program, Chief Clinical Officer for Ambulatory Care, and Director of the Cancer Network.
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Thomas Marron, MD, PhD, has been appointed as Director of the Early Phase Trials Unit at The Tisch Cancer Institute. Dr. Marron has been instrumental in the growth of the unit to date and will oversee the next phase of expansion of early phase clinical drug development initiatives.
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Alessandro Lagana, PhD, has transferred from the Department of Genetics & Genomic Sciences to the Department of Oncological Sciences, where he will focus on computational genomics and precision medicine for multiple myeloma.
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Christian Rolfo, MD, PhD, MBA, Dr.hc. will join Mount Sinai on June 1 as Professor of Medicine (Hematology and Medical Oncology) and Associate Director for Clinical Research in the Center for Thoracic Oncology at The Tisch Cancer Institute. Dr. Rolfo’s clinical and research focus is on drug development, lung cancer and other thoracic malignancies, biomarkers, resistant mechanisms discovery, and liquid biopsies. Dr. Rolfo has held academic appointments at numerous institutions, including the University of Cordoba, Argentina; University of Antwerp, Belgium; and University of Palermo, Italy. He comes to Mount Sinai from the University of Maryland and Greenbaum Comprehensive Cancer Center in Baltimore where he was Director of Thoracic Medical Oncology and Director of Early Clinical Trials. Dr. Rolfo earned his MD at the University of Cordoba School of Medicine, his PhD and Doctor Europaeus in Clinical Oncology and Experimental Research at European University of Palermo, and an MBA in Hospital and Health Services Management and Organization at Polytechnic University of Valencia, Spain. He completed residency training in Medical Oncology at the National Cancer Institute in Milan. Dr. Rolfo is Vice President of the International Society of Liquid Biopsy (ISLB) and Deputy chair of the Education Committee at the International Association for Study of Lung Cancer (IASLC). Dr. Rolfo served as member of the Drug Approval & First in Human Commission at the Ministry of Health in Belgium during his time as Phase I Director at Antwerp University. He has published more than 250 papers and received numerous accolades.
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Diego Chowell, PhD, has joined Mount Sinai as Assistant Professor of Oncological Sciences. In collaboration with the Precision Immunology Institute, his lab is focused on challenges at the intersection of computational immunology, cancer immunogenomics, and cancer immunotherapy. Dr. Chowell earned his PhD in applied mathematics from Arizona State University with a research emphasis on mathematical and computational models of cancer and the immune system. He earned a Master’s degree from Utrecht University, The Netherlands, where he worked on dynamical systems and chaos theory. Dr. Chowell spent a year as a visiting graduate student at the Moe Win Laboratory for Information and Decision Systems at MIT. He was most recently a postdoctoral research fellow in the Timothy Chan Lab at Memorial Sloan Kettering Cancer Center.
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Stand Up To Cancer® (SU2C) has awarded funding for its first team of researchers dedicated to health equity in cancer research. The SU2C Health Equity Breakthrough Team, led by Nina Bickell, MD, will address the low participation of Black, Indigenous and People of Color in cancer clinical trials.
The team will focus on:
- Working with community organizations to raise awareness about cancer research;
- Training scientists and doctors about the importance of engaging with and including a diverse group of patients in cancer research;
- Exploring ways to better inform underrepresented patients about clinical trials.
“Much of our standard of care in cancer is grounded in research with mostly white populations,” said Dr. Bickell. “Our goal is to figure out how we can change that —in how scientists approach their work, how medically underserved communities can learn more about pioneering cancer research and treatments and how care delivery systems can make it easier for patients to learn about clinical trials.”
The other members of the team are co-leader Karen Hubbard, PhD, professor of biology at The City College of New York; Bruce Rapkin, PhD, associate director of community outreach and engagement at the Albert Einstein Cancer Center and professor of epidemiology and population health at Albert Einstein College of Medicine; and Mary Beth Terry, PhD, associate director for population science and community outreach at Columbia University’s Herbert Irving Comprehensive Cancer Center.
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Julio Aguirre-Ghiso, PhD, received an R03 grant award from the National Cancer Institute for “Immune Regulation of Disseminated Cancer Cell Dormancy.” This is his first immunotherapy-related grant award. The overarching goal of the research is to uncover mechanisms involved in the interaction between dormant disseminated cancer cells and the immune system and therefore reveal therapeutic opportunities for minimal residual disease before the development into a full-blown lethal disease.
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Jian Jin, PhD, and Hong Wen, PhD, at Van Andel Research Institute have received a five-year R01 grant from the National Cancer Institute to develop novel therapeutics for treating mixed-lineage leukemia (MLL)-rearranged leukemias. Patients with rearrangements of the MLL gene often have a dismal prognosis. Dr. Jin, Dr. Wen, and team will develop first-in-class PROTAC degraders of ENL, an MLL fusion partner, as a novel therapeutic strategy.
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Letter of Intent due date: June 29, 2021
Letter of Intent due date: July 6, 2021
Letter of Intent due cate: August 1, 2021
Letter of Inquiry Deadline: August 2, 2021
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Clinical Cancer Research. 2021 Apr 9. PMID: 33837006
This study identified validated key gene signatures associated with sensitivity or resistance to checkpoint inhibitors in patients with metastatic urothelial cancer. It showed that the balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance, with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood.
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Hepatology Communications. 2021 Mar 23.
This study demonstrated the feasibility of modeling liquid biopsy in hepatocellular carcinoma xenografts and identified cell clone origin as a potential major determinant of DNA fragment release into the bloodstream. The research showed tumor clone‐dependent rates of circulating tumor DNA (ctDNA) detection, ctDNA dynamics following systemic therapy, and the role of circulating tumor cell detection to predict clinical endpoints, such as the development of distant metastasis.
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Nature. 2021 Mar 24. PMID: 33762733
This study shows that non-viral hepatocellular carcinoma (HCC), and particularly HCC driven by non-alcoholic steatohepatitis (NASH), might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. The data provide a rationale for stratification of patients with HCC according to underlying etiology in studies of immunotherapy as a primary or adjuvant treatment.
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Developmental Cell. 2021 May 3. PMID: 33887204
This review examines the mechanistic contributions of mitochondria to regulated cell death (RCD) signaling and how mitochondria participate in the production and presentation of key macromolecules and platforms that actively enable, initiate, and execute RCD. Further understanding of the relationships between mitochondria and RCD may present prognostic and therapeutic opportunities.
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Cancer. 2021 Mar 18. PMID: 33735504
This phase 1b study demonstrated that isatuximab in combination with carfilzomib is well tolerated in patients with relapsed and refractory multiple myeloma and has excellent potential for the treatment of patients with disease that is refractory to immunomodulatory drugs and proteasome inhibitors.
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Blood Advances. 2021 Mar 23. PMID: 33710339
This study identifies a new and simple approach for isolating highly potent human hematopoietic stem cells (HSCs) and implicates mitochondria in the intrinsic regulation of human HSCs’ quiescence and potency. Findings suggest that reduced mitochondrial activity and network organization in human HSCs are indicators of prolonged quiescence and select for HSCs with long-lasting in vitro and in vivo activity.
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Cell Stem Cell. 2021 Mar 4. PMID: 33667358
This paper discusses a newly discovered and fundamental role of lysosomes in controlling the neural and hematopoietic stem cell switch between quiescent and active states and the potential of exploring lysosomal properties for clinical purposes.
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Future Oncology. 2021 Mar 12. PMID 33706558
This review discusses the management of patients with multiple myeloma whose disease is difficult to treat due to the propensity for multiple relapses, cumulative and emergent toxicities from prior therapies, and increasing genomic complexity resulting from clonal evolution.
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Communications Biology. 2021 Jan 29. PMID: 33514835
The researchers demonstrated that glioblastoma cells gain invasiveness—a major cause of high lethality of malignant brain tumors—by upregulating guidance receptor Plexin-B2. They highlighted complex physical interactions of invading tumor cells with their environment and unraveled three underlying biomechanical mechanisms by which Plexin-B2 exerts its function to promote glioblastoma invasion.
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Proceedings of the National Academy of Sciences USA. 2021 Apr 6. PMID: 33785595
This study reveals that autophagy selectively degrades PKA inhibitory subunit RIα through new autophagy receptor AKAP11 in response to energy crisis, causing PKA activation. This suggests that tumor cells may exploit such a metabolic reprogramming mechanism for oncogenic growth, and that AKAP11-mediated cAMP/PKA activation via selective autophagy might be a therapeutic target for cancer treatment.
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Hematology/Medical Oncology Grand Rounds, Thursdays at 8:30 am
"Targeting DNA damage response pathways in prostate cancer""
Translational Oncology Seminar, Fridays at 12 noon
TCI Seminar Series, Tuesdays at 12 noon
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Cancer and Aging Program (CAP) Annual Retreat
May 17, 11 am – 3 pm
This retreat will provide opportunities to explore potential collaborations to improve health outcomes of cancer patients, and will focus on new and innovative areas for cancer and aging research including genetics/genomics, cancer biology, clinical trials, and macrophages in aging and cancer.
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Survivors Day Virtual Celebration
June 6, 2021, 11 am – 12 noon
Hosted by Alison Snow, LCSW-R, OSW-C, and Kaitlin Goldgraben, LCSW
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2021 Summer Research Scholars
Two medical students at the Icahn School of Medicine at Mount Sinai will participate in the TCI Medical Student Research Fellowship program, designed to provide opportunities to conduct original cancer research for medical students who have not yet had extensive research experience. The 2021 scholars and their faculty mentors are:
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Do you have news for the next issue of TCI Connections?
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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Ramon Parsons, MD, PhD, Director
Janet Aronson , Editor
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