The focus of my current research is to understand mechanisms of cellular signaling at the level of the primary cilia, and its relevance to human health and disease. As a starting assistant professor at the Department of Cell Biology at UT Southwestern, my current and future research aims at utilizing a variety of biochemical, cell biological, and reverse genetic approaches to investigate signaling pathways mediated by cilia, and to dissect their role during normal development and disease. During my graduate years in Dr. Piali Sengupta’s lab at Brandeis University, I utilized C. elegans to study the mechanisms that determine the distinctive ciliary morphology of their sensory neurons, and discovered that the membrane architecture of the olfactory sensory cilia is patterned by coincidental signaling inputs. In my postdoctoral years in Dr. Peter Jackson’s lab in Genentech, I used high-confidence proteomic approaches to study ciliary signaling pathways. In particular, our identification of the tubby family protein Tulp3 as an effector of the ciliary intraflagellar complex A (IFT-A), and in regulating ciliary G protein-coupled receptor (GPCR) trafficking provides intriguing insights into molecular mechanisms regulating ciliary function in diverse processes, such as in sonic hedgehog (Shh) signaling during neural tube development and in neuronal control of obesity. Most importantly, we have identified a novel Tulp3/IFT-A–regulated ciliary GPCR, Gpr161 that acts as a negative regulator of Shh signaling in the neural tube via cAMP signaling.
Currently, we are determining mechanisms underlying trafficking of signaling molecules in and out of cilia and the phenotypes resulting from changes in ciliary trafficking. In addition, we are heavily invested in understanding the role of primary cilia at an organismal level. To this end, we are determining the role of primary cilia signaling in limb and skeletal development, polycystic kidney disease, neural tube defects, and tumorigenesis. Our results demonstrate that basal suppression of the downstream hedgehog pathway by Gpr161, even in the absence of morphogen is critical in regulating limb/skeletal development and cerebellar tumorigenesis. Overall, our expertise in Shh signaling and its regulation by cilia, our demonstrated strengths in utilizing a multi-pronged approach including proteomics, cell biology, and reverse genetics to discover novel Shh pathway regulators, including the discovery of the Tulp3-Gpr161 axis, and further engineering of conditional knock out and knock in alleles targeting these factors, uniquely position us to determine the role of basal suppression of Shh signaling in these diverse processes. Finally, the collaborative nature of research and the strong focus on translational biomedical research at UT Southwestern is instrumental for studying these diverse developmental paradigms aiming at understanding the role of primary cilia in development and disease.
- (1998), Medicine
- Medical School
- Banaras Hindu University (2002), Medicine
- Graduate School
- Brandeis University (2008), Biology
- Ciliary signaling pathways
- Functional proteomics in ciliary diseases
- Primary cilia in normal development and cancer
- Basal Suppression of the Sonic Hedgehog Pathway by the G-Protein-Coupled Receptor Gpr161 Restricts Medulloblastoma Pathogenesis.
- Shimada IS, Hwang SH, Somatilaka BN, Wang X, Skowron P, Kim J, Kim M, Shelton JM, Rajaram V, Xuan Z, Taylor MD, Mukhopadhyay S Cell Rep 2018 Jan 22 5 1169-1184
- The G-protein-coupled receptor Gpr161 regulates forelimb formation, limb patterning and skeletal morphogenesis in a primary cilium-dependent manner.
- Hwang SH, White KA, Somatilaka BN, Shelton JM, Richardson JA, Mukhopadhyay S Development 2017 Dec
- Tubby family proteins are adapters for ciliary trafficking of integral membrane proteins.
- Badgandi HB, Hwang SH, Shimada IS, Loriot E, Mukhopadhyay S J. Cell Biol. 2017 Feb
- Trafficking to the primary cilium membrane.
- Mukhopadhyay S, Badgandi HB, Hwang SH, Somatilaka B, Shimada IS, Pal K Mol. Biol. Cell 2017 Jan 28 2 233-239
- Smoothened determines ß-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium.
- Pal K, Hwang SH, Somatilaka B, Badgandi H, Jackson PK, DeFea K, Mukhopadhyay S J. Cell Biol. 2016 Mar
- G-protein-coupled receptors, Hedgehog signaling and primary cilia.
- Mukhopadhyay S, Rohatgi R Semin. Cell Dev. Biol. 2014 May
- The Ciliary G-Protein-Coupled Receptor Gpr161 Negatively Regulates the Sonic Hedgehog Pathway via cAMP Signaling.
- Mukhopadhyay S, Wen X, Ratti N, Loktev A, Rangell L, Scales SJ, Jackson PK Cell 2013 Jan 152 1-2 210-223
- TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia.
- Mukhopadhyay S, Wen X, Chih B, Nelson CD, Lane WS, Scales SJ, Jackson PK Genes Dev. 2010 Oct 24 19 2180-93
- Cellular signalling by primary cilia in development, organ function and disease.
- Anvarian Z, Mykytyn K, Mukhopadhyay S, Pedersen LB, Christensen ST Nat Rev Nephrol 2019 Feb
- Dominant negative GPR161 rare variants are risk factors of human spina bifida.
- Kim SE, Lei Y, Hwang SH, Wlodarczyk BJ, Mukhopadhyay S, Shaw GM, Elizabeth Ross M, Finnell RH Hum. Mol. Genet. 2018 Sep
Honors & Awards
- Alexs Lemonade Stand Foundation A grant awardee
- W.W. Caruth, Jr. Scholar in Biomedical Research
Endowed scholar, UT Southwestern (2013)
- CPRIT Scholar in Cancer Research.
- Member, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center. (2013)
- American Society for Cell Biology. (2005)