Five teams led by Weill Cornell Medicine scientists have been awarded funding from the Starr Cancer Consortium in its sixteenth annual grant competition. The grants will fund research on the molecular origins and evolution of blood, bladder, breast, and colon cancers.
The Starr Cancer Consortium was established in 2006 through the philanthropy of the Starr Foundation, and includes The Broad Institute of MIT and Harvard, Cold Spring Harbor Laboratory, Memorial Sloan Kettering Cancer Center, The Rockefeller University and Weill Cornell Medicine. The goal of the consortium is to support collaborative research at these institutions, with the potential to rework the understanding and treatment of cancers.
Collaboration is at the guts of the Meyer Cancer Center. As we learn through studying various modern treatment modalities, and with interdisciplinary engagement, we are able to see similarities between diseases and apply therapies more broadly. This award will help us move the needle on cancer diagnosis and look after the good thing about patients in our catchment area and globally. We’re so grateful to the Starr Foundation for its generous support.”
Dr. Jedd Wolchok, the Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine
Collaborative projects proposed by Drs. Steven Josefowicz, Dawid Nowak, Melody Zeng, Lukas Dow and Bishoy Faltas were chosen for funding by a scientific review board of peers from institutions outside the consortium.
“We’re grateful for the generosity of the Starr Foundation, which supports these ambitious efforts to advance cancer research and patient care,” said Dr. Hugh Hemmings, senior associate dean for research and chair of the Department of Anesthesiology at Weill Cornell Medicine. “We’re very proud to see such strong support by the Starr Foundation this yr for Weill Cornell Medicine investigators’ projects.”
Dr. Steven Josefowicz
Associate Professor of Pathology and Laboratory Medicine
Mechanisms of dynamic chromatin reorganization regulating B-cell differentiation and lymphomagenesis (renewal of prior award)
In response to an infection, some B cells, which make antibodies, undergo a phase of hyper-mutation and proliferation. The aim of this process, which takes place in a lymph node region called the germinal center, is to spice up the range of the antibodies that may bind to the invading pathogen, making the response simpler. But this process also puts B cells on the point of turning cancerous, and indeed many lymphomas arise from germinal center B cells, apparently attributable to a failure of normal regulatory systems in these cells. Dr. Josefowicz and colleagues are pursuing the hypothesis that certainly one of these failures is akin to a stuck gas pedal for a pathway involving the phosphorylation of DNA packaging histones called histones, a process that potently prompts genes controlling growth and lymphomagenesis-;and that blocking this process with the best drugs could send some aggressive lymphomas into swift remission.
Co-Principal Investigators: Dr. Christina Leslie (Memorial Sloan Kettering Cancer Center), Dr. Ari Melnick (Weill Cornell Medicine) and Dr. Shixin Liu (The Rockefeller University).
Dr. Dawid Nowak
Assistant Professor of Pharmacology in Medicine
Determining and targeting evolutionary trajectories driving bladder cancer
Muscle-invasive bladder cancer (MIBC), so-called since it has invaded the bladder muscle, is difficult to treat successfully. The dearth of fine treatments is attributable to the relatively poor scientific understanding of how MIBC arises. Dr. Nowak and his team are attempting to enhance this understanding with the assistance of a latest, sophisticated model of MIBC in mice. Tumors within the model are driven by genetic mutations ceaselessly observed in human MIBC, and might recapitulate metastasis to lymph nodes, all in mice with intact immune systems. The model also employs a DNA “evolving barcode” for the detailed tracking of MIBC evolution. The researchers will use the mice to generate ideas for brand spanking new treatments, and ultimately to check those treatments.
Co-Principal Investigators: Dr. David Solit (Memorial Sloan Kettering Cancer Center) and Dr. Adam Siepel (Cold Spring Harbor Laboratory).
Dr. Melody Zeng
Assistant Professor of Immunology in Pediatrics
Defining the role of stress-induced changes within the IgG-gut microbiome-neutrophil axis during breast cancer progression and metastasis
Dr. Zeng and her collaborators are studying interactions/crosstalk between IgG-type antibodies, white blood cells called neutrophils, and bacteria that dwell within the human gut that might promote cancer and its spread to distant organs. The researchers have found evidence that chronic stress, a deficiency of IgG antibodies, and/or the presence of certain gut bacteria, can perturb this signaling axis in a way that results in immune suppression and cancer progression in mouse models of cancer, including breast cancers. They expect to translate their novel findings into latest treatment strategies for breast cancer, potentially including vaccines against specific gut bacteria.
Co-Principal Investigators: Dr. Irina Matei (Weill Cornell Medicine) and Dr. Mikala Egeblad (Cold Spring Harbor Laboratory).
Dr. Lukas Dow
Associate Professor of Biochemistry in Medicine
Identifying acquired vulnerabilities driven by lineage plasticity and drug resistance in CRC
Traditionally, research on the mechanisms of cancer progression has focused on latest DNA mutations in cancer cells as key sources of enhanced malignancy. But cancer biologists increasingly recognize that non-mutational mechanisms controlling the patterns of gene activity in cells are also in charge, including proliferative mechanisms which might be normally seen only within the fetal stage of life, or in wound healing. On this project, Dr. Dow and his collaborators will examine a few of these mechanisms and their roles and interactions-;and vulnerabilities-;in colorectal cancer treatment resistance and metastasis.
Co-Principal Investigator: Dr. Karuna Ganesh (Memorial Sloan Kettering Cancer Center)
Dr. Bishoy Faltas
Assistant Professor of Cell and Developmental Biology; Director of Bladder Cancer Research on the Caryl and Israel Englander Institute for Precision Medicine; and a member of the Sandra and Edward Meyer Cancer Center
Targeting cytidine deaminase-induced chromosomal instability as a driver of metastasis in bladder cancer
APOBEC3 enzymes, that are produced widely in human cells, have the curious property that they induce mutations in DNA. That is at the very least partly to defend against infecting retroviruses, equivalent to HIV, and cells are thought to have safety mechanisms for shielding their chromosomal DNA from these enzymes. Nevertheless, Dr. Faltas and other researchers have been finding evidence in recent times that these enzymes are co-opted by some cancers, including bladder cancers, to spice up their mutation rates-;making it easier for them to evolve. On this project, they may explore APOBEC3s’ roles in driving bladder tumor metastasis, in addition to the potential for targeting these enzymes to forestall metastasis.
Co-Principal Investigators: Dr. Samuel Bakhoum (Memorial Sloan Kettering Cancer Center) and Dr. Vivek Mittal (Weill Cornell Medicine).