Sunil Sukumaran Assistant Professor of Molecular Genetics
Ph.D, Genetics, University of Cologne, Cologne, Germany, 2005
M.Sc., Biotechnology, Cochin University of Science and Technology, Cochin, India, 1998
B.Sc., Zoology, University of Calicut, Calicut, India, 1996
The taste system is the first to physically encounter ingested food and is in many ways a gatekeeper of nutrition. Unhealthy eating habits, such as the overconsumption of sugars, fats and salt are the major causes of lifestyle diseases such as obesity, diabetes and hypertension. Taste buds, located primarily on the surface of the tongue but also on other locations in the oral cavity such as the soft palate, contain several types of taste receptor cells that sense and transduce taste signals. Like other cells of the lingual epithelium, they are short lived, with half-lives ranging between 12-24 days. The receptors and downstream signaling components for sweet, bitter, low salt, sour and umami taste qualities are known, while those for high salt remain unidentified. Taste nerves carry taste signals from taste cells to the gustatory cortex through a relatively well defined (at least in rodents) neural pathway, that gives rise to taste guided behaviors. How the taste system with its diversity of receptors and cell types maintain a stable functional profile through out the lifespan in spite of constant turnover of taste cells is poorly understood. We aim to identify pathways regulating taste signaling and taste cell regeneration, and to apply these findings to develop novel strategies to promote healthy eating habits. Current projects in the lab include:
Identification of taste signaling pathways: Although the receptors and downstream signaling molecules for almost all primary taste qualities have been identified, several questions pertaining to taste signaling pathways remain open. For e.g., although taste adaptation is well recognized in literature, the mechanisms that regulate taste signaling pathways and lead to adaptation are not known. It is also likely that more than one signaling pathway mediate responses to any particular taste quality. A case in point is that of the sweet taste signaling. The heterodimer formed by the G-protein coupled receptor subunits TAS1R2 and TAS1R3 is the primary receptor for sweet taste. We recently identified a T1R independent pathway tuned to caloric sugars and starch in the same taste cells that express the sweet taste receptor. This pathway is similar to that expressed in tissues such as the intestine and pancreas and requires the concerted action of enzymes that hydrolyze starch and disaccharides (the alpha glucosidases), glucose transporters and the ATP- sensitive potassium channel, KATP. We are now studying how both these pathways work together and are regulated to generate the sweet taste percept.
Similar to sugars, fat is a macronutrient with vital physiological roles. Surprisingly, it is not clear if or how fats are sensed by taste cells; indeed, the concept of fat taste itself remains controversial. Some candidate fat taste receptors, namely GPR120 and CD36 have been identified, but conclusive proof for their role in fat taste signaling is lacking. We are looking at the role of candidate fat sensing pathways identified in other tissues in fat taste signaling using knockout and other mouse models.
Pathways regulating taste cell diversity and regeneration: At present, taste cells are subdivided into about half a dozen subtypes based on morphological and functional criteria. However, it is very likely that there are as yet unidentified, functionally important taste cell types. Further, the trajectory of taste cell regeneration and the key signaling pathways and transcription factors that orchestrate this program remain largely unidentified. We used droplet based single cell RNA-Seq of thousands of taste cells to identify novel taste cell types and pathways regulating taste cell diversification. The results confirmed the existence of several novel taste cell types. We are doing follow up studies using cell ablation and other approaches in mice models to identify the function of the newly identified taste cell populations. Taste cell regeneration is perturbed by conditions such as chemotherapy, autoimmune diseases, aging and dietary deficiencies. In future studies, we will use scRNASeq and spatial RNS-Seq in mouse models of the above conditions to identify the signaling and transcriptional pathways dysregulated in these conditions.
Yumei Qin, Sunil K. Sukumaran, Masafumi Jyotaki, Kevin Redding, Peihua Jiang, Robert F. Margolskee (2018). Gli3 is a negative regulator of Tas1r3-expressing taste cells. PLoS Genet 14(2): e1007058
Sunil K. Sukumaran, Brian C. Lewandowski, Alexander A. Bachmanov, Robert F. Margolskee. Whole transcriptome analysis of taste bud cells. Sci Rep. 2017 Aug 8;7(1):7595.
Sunil K. Sukumaran, Karen K. Yee, Shusuke Iwata, Ramana Kotha, Roberto Quezada-Calvillo, Buford L. Nichols, Sankar Mohan, B. Mario Pinto, Noriatsu Shigemura, Yuzo Ninomiya and Robert F. Margolskee (2016). Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides. Proc Natl Acad Sci U S A. 2016 May 24;113(21):6035-40.
Brian C. Lewandowski, Sunil K. Sukumaran, Robert F. Margolskee and Alexander A. Bachmanov (2016). Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms. J Neurosci. 2016 Feb 10;36(6):1942-53.
Karen K. Yee, Sunil K. Sukumaran, Ramana Kotha, Timothy A. Gilbertson and Robert F. Margolskee (2011). Glucose transporters and ATP-gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells. Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5431-6.