Research Seminar Speaker Series – Atish Mohanty, City of Hope – “A Systems Biology Perspective on the Development of Drug Resistance”

Please join us for our Research Seminar Series Speaker, Atish Mohanty, Assistant Research Professor Department of Medical Oncology at City of Hope National Medical Center on:

The increasing incidence of cancer and the challenge posed by drug resistance highlights the need for a comprehensive understanding of the molecular mechanisms involved in resistance development. My research is focused on investigating the genetic and non-genetic mechanisms of drug resistance in various cancer models and identifying alternative strategies to overcome the resistant phenotype. We identified novel mutations in the cyclin D1 proto-oncogene, leading to the development of resistance against ibrutinib in mantle cell lymphoma. We also highlighted the role of secondary mutations such as STK11, PI3K, or CTNNB1 mutations in developing resistance against KRAS-G12C inhibitors in lung cancer. In addition to genetic mechanisms, we explored the non-genetic mechanisms of drug resistance, revealing the significance of paxillin (PXN) and integrin β4 (ITGB4) interaction in developing cisplatin resistance in lung adenocarcinoma. We studied the cancer cell behavior and proposed a phenotypic switching mathematical model that captures the dynamic behavior of cooperation and competition among sensitive and resistant cells in a heterogeneous system. The model explains the dynamic phenotypic plasticity of ITGB4-expressing lung cancer cells, transitioning from a low-expressing state to a high-expressing state or vice versa. The dynamic behavior of cells was utilized to develop an intermittent therapeutic strategy instead of the usual continuous therapeutic strategy. Overall, the current research offers new insights into the molecular mechanisms of drug resistance in cancer and provides alternative strategies to overcome the development of resistant phenotypes, opening new avenues for developing effective therapeutic interventions.

Friday:  March 3, 2023

Time:  12:00 – 1:00 p.m.

Location:  121 Bldg. – 1111 classroom & Via Zoom (See Outlook invite for Zoom Link)