Grant to focus on developing engineered experimental therapeutics technologies to understand the mechanism of resistance in diffuse large B cell lymphoma (DLBCL) and enable the translation of a new therapeutic to treat cancer patients better.
Ankur Singh, an Associate Professor of George W. Woodruff School of Mechanical Engineering at Georgia Institute of Technology and Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, has been awarded a five-year, $2.3 million RO1 grant from the National Cancer Institute of the National Institutes of Health (NIH) as PI. The R01 focuses on developing engineered experimental therapeutics technologies to understand the mechanism of resistance in diffuse large B cell lymphoma (DLBCL) and enable the translation of a new therapeutic to treat cancer patients better.
Approximately 40% of patients with activated B cell (ABC) subtype of DLBCL relapse or are not curable with current therapies. Singh, a new hire at Georgia Tech, has been working for the past 7 years to understand how the resistance to current therapies is linked to the spectrum of cancer cell mutations in these tumors and their concert with complex growth signals provided by the tumor microenvironment. Singh and his long-time collaborator, Ari Melnick, the Laurel Gebroe Family Professor of Hematology/Oncology at Weill Cornell Medicine in New York, have been investigating the effect of tumor microenvironment on a unique therapeutic target, Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) protein, in DLBCLs. The R01 will elucidate a better understanding of MALT1 therapeutic response in patient samples and enable its translation.
“Prior targeted therapies, such as Ibrutinib, the Bruton Tyrosine Kinase (BTK) inhibitors, only work in a fraction of patients. We believe MALT1 has a stronger potential, and as the first-in-human MALT1 targeting clinical trial recently began accruing patients, identifying putative resistance and feedback mechanisms against MALT1 inhibitor is critically important,” says Singh.
Singh is developing lymph node-like organoids and on-chip technologies, which provide a unique platform to study patient tumors. He has combined his biomaterials engineering and immune-engineering expertise with Melnick’s translational cancer therapy to innovate Lymphoma-on-chip and organoid technology, which can grow patient tumors in a controlled lymph node-like microenvironment. The technology includes an organoid growing chamber connected to a media (fluid) chamber by narrow resistance channels, which slowed the fluid to mimic the flow inside lymph vessels and parts of the lymph node. The proposal further integrates expertise in the immunology of Cynthia Leifer, imaging of Chris Xu, and systems biology of Benjamin Cosgrove, all at Cornell University where Singh was previously an associate professor.
“We are truly grateful to the NIH/NCI for the funding support,” said Singh. “The grant support allows us to define how the underlying biology of lymphoma cells is linked to the host microenvironment’s immunological and biophysical properties, which is poorly understood in hematological malignancies.”
Prior to joining Georgia Tech, Singh was an Associate Professor of Mechanical Engineering and Biomedical Engineering at Cornell University, Ithaca, NY. At Cornell, he was a member of the Englander Institute for Precision Medicine at Cornell Medicine (NYC). He had affiliations with Cornell’s Immunology and Infectious Disease Program. He served on the Executive Council of Cornell Center for Immunology. He was on Cornell’s advisory council for academic integration across Ithaca and NYC campuses. He joined Cornell University in 2013 after his postdoctoral training in cell mechanobiology, cell-matrix interactions, and stem cell engineering at Georgia Tech and Ph.D. in Biomedical Engineering at The University of Texas at Austin.
His “Immunotherapy and Cell Engineering” laboratory at Georgia Tech is developing strategies to engineer adaptable, designer immune organoids and enabling technologies for the mechanistic understanding of healthy and diseased immune cells. He has received funding from the National Institute of Health (NIAID, NCI), National Science Foundation, Department of Defense, and the Lymphoma and Leukemia Society, among others. He is a recipient of several scientific awards (including the NSF CAREER, 3M Non-Tenured Faculty Award, and the DoD Career award) and Cornell Engineering ‘s Teaching Excellence Award. His immune organoids research has been identified among Top 100 Discoveries of 2015 by the Discover Magazine. he Discover Magazine.