Tirtha K Das, PhD

Tirtha Kamal Das, PhD, is an Assistant Professor in the Department of Cell, Developmental & Regenerative Biology, and at The MINDICH Child Health and Development Institute.

He obtained his PhD degree at Wesleyan University studying the developmental genetics of fly embryogenesis and later completed his postdoctoral work modeling cancer and therapeutics in flies. He has continued his interest in understanding human disease and his lab uses an ‘Integrated Fly-Vertebrate Modeling’ approach to study genetic diseases and identify novel therapeutics. They use whole animal fly models, human cell lines, mouse xenografts, and patient data analysis to identify mechanisms of cancer and Mendelian disease progression.

These studies have identified key cellular and molecular mechanisms driving cancer progression, and have shown that: i) oncogenic kinase-gene fusions drive complex signaling through multi-protein hubs, ii) epigenetic components promote programs of cancer cell invasion, and iii) centrosomal components promote metastasis.

His lab combines genetics and drug screening to rationally improve lead compounds and clinical therapeutics. They showed that optimal therapeutic index of cancer drugs is achieved through balanced inhibition of multiple targets – balanced polypharmacology. They further developed drug cocktails to improve therapeutic index of standard of care drugs, by pairing them with low-dose, broad-acting drugs – ‘network brakes’ – that prevented compensatory activation of cellular networks, which lowered toxicity, and delayed emergence of drug resistance.

This integrated approach has also been applied to study dominant Mendelian-inherited human Rasopathies and identified signaling differences between thirteen variants, and uncovered unique opportunities for therapy. Drugs inhibiting epigenetic components and treatments used for cardiovascular diseases have shown surprising efficacy in these Rasopathy models.