My research program to date has contributed to our fundamental understanding of how changes in ‘receptor structure leads to function’. Using specialized quantitative imaging techniques with complementary cell and molecular biology approaches both in vitro and in vivo, I have uncovered novel ways by which the cytokine receptor, Growth Hormone Receptor (GHR), regulates several biological functions in normal physiology and cellular dysfunction. GHR is expressed in every physiological system of the body and any aberrant signaling owing to internal factors (genetic) or external factors (environment) or both can result in cellular dysfunction. I deciphered the mechanism of the first single nucleotide polymorphism of GHR associated with increased susceptibility to lung cancer. Concurrently, my work described the mechanism of anti-insulin effects of Growth Hormone, a phenomenon that has remained elusive for 50 years. Using innovative mouse models with delineated GHR signaling I showed impaired gluconeogenesis and glucose metabolism via GH-mediated JAK2/STAT5 action. A critical attribute of calorie restriction or intermittent fasting is reduction of GH and improvement of insulin sensitivity which is where my research fills the gap. Subsequent to my PhD in GHR biology, my postdoctoral research has shed light on the effect of single nucleotide polymorphisms in pigmentation genes (IRF4, MTAP and PLA2G6) on melanocytic biology as well as the role of MITF and BRN2 transcription factors in ‘melanoma phenotype switching’ and role of orphan nuclear receptor NR4As in DNA repair.

In the Weeraratna Laboratory, I undertook how sex as well as the age of the host microenvironment guides metastasis, dormancy, and therapy resistance in melanoma. Using a unique resource of normal skin fibroblasts from healthy donors stratified by age across both the sexes and utilizing animal models, my research program aims to determine the metabolic, biophysical, and biochemical changes that affect the communication between tumor, stromal and immune cells thereby regulating metastasis and therapeutic responses. The implications of these data will ultimately result in change in the current clinical practice. My long-term research goal as an independent investigator is in precision oncology by taking a holistic approach and incorporating gender medicine and geroscience.