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Mukhopadhyay, Somshuvra

Somshuvra Mukhopadhyay

Associate Professor
College of Pharmacy

James E. Bauerle Centennial Professorship in Drug Dynamics (Fellow)

neurologic diseases, membrane trafficking, infectious diseases, ion homeostasis, drug discovery

som@austin.utexas.edu

Phone: 512-232-8200

Office Location
BME 3.510E

Postal Address
107 W DEAN KEETON ST
AUSTIN, TX 78712

Current:

Associate Professor
Division of Pharmacology & Toxicology; Institute for Cellular & Molecular Biology; and Institute for Neuroscience,
The University of Texas at Austin
Austin, TX 78712.

 

Education & Training:

1. Post-doctoral Fellow with Dr. Adam Linstedt: Carnegie Mellon University, Pittsburgh, PA. Aug 2008 - Jan 2013.

2. Ph.D. in Cell Biology with Dr. Pravin Sehgal: New York Medical College, Valhalla, NY. Aug 2004 - May 2008.

3. M.B.B.S. (Bachelor of Medicine, Bachelor of Surgery): Topiwala National Medical College, Mumbai, India. Aug 1998 - April 2004 (M.B.B.S. is equivalent to M.D. in the USA).

 

Research Interest:  The focus of our studies is to understand the mechanisms of, and devise treatments for, incurable human diseases. Currently, we have two major projects that bridge neuroscience, cell biology, infectious diseases, and drug discovery.

1. Gene-environment interactions in parkinsonism: We seek to understand the mechanisms by which genetic mutations and environmental insults come together to cause parkinsonian disorders. Our specific focus is on genes that regulate levels of essential metals, such as iron, manganese, and copper - these metals are required for normal neuronal function, but cause severe neurotoxicity at elevated levels. Our major goals are to understand how cells and organisms maintain homeostatic control of essential metals in the brain, and how changes in these homeostatic pathways, secondary to genetic mutations and environmental insults, result in parkinsonism.

2. Intracellular trafficking of Shiga and related bacterial toxins: Bacteria that produce Shiga and related toxins affect millions each year. Antidotes for these toxins are not available, and this severely limits treatment options. The goals of this project are to determine the mechanisms by which these bacterial toxins invade cells to cause disease, and to design therapeutically viable small molecule inhibitors of toxin transport.

Please view our lab website to read more about our research, publications, and available positions. 

Publications relevant to on-going work in the lab:

 Trainees in the laboratory are in italics. Asterisks denote corresponding author.

  1. Taylor CA, Shawlot W*, Ren JX, Mukhopadhyay S*. Generation and validation of tissue-specific knockout strains for toxicology research. Curr Protoc Toxicol 81: e86, 2019.
  2. Selyunin AS, Hutchens S, McHardy SF, Mukhopadhyay S*. Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosis. Life Sci Alliance 2: e201900439, 2019.
  3. Taylor CA, Mukhopadhyay S*. Transporter Studies: Brain Punching Technique. Neuromethods 145: 245-253, 2019.
  4. Li D, Mukhopadhyay S*. Functional analyses of the UDP-galactose transporter SLC35A2 using the binding of bacterial Shiga toxins as a novel activity assay. Glycobiology 29: 490-503, 2019.
  5. Taylor CA, Hutchens S, Liu C, Jursa T, Shawlot W, Aschner MA, Smith DR, Mukhopadhyay S*. SLC30A10 transporter in the digestive system regulates brain manganese under basal conditions while brain SLC30A10 protects against neurotoxicity. J Biol Chem 294: 1860-1876, 2019.
  6. Carmona A, Zogzas CE, Roudeau S, Porcaro F, Garrevoet J, Spiers K, Salome M, Cloetens P, Mukhopadhyay S, Ortega R. SLC30A10 mutation involved in parkinsonism results in manganese accumulation within nano-vesicles of the Golgi apparatus. ACS Chem Neurosci 10: 599-609, 2019.
  7. Zogzas CE, Mukhopadhyay S*. Putative metal binding site in the transmembrane domain of the manganese transporter SLC30A10 is different from that of related zinc transporters. Metallomics 10: 1053-1064, 2018.
  8. Selyunin AS, Iles LR, Bartholomeusz G, Mukhopadhyay S*. Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking. J Cell Biol 216: 3249-3262, 2017.
  9. Liu C, Hutchens S, Jursa T, Shawlot W, Polishchuk EV, Polishchuk RS, Dray BK, Gore AC, Aschner M, Smith DR, Mukhopadhyay S*. Hypothyroidism induced by loss of the manganese efflux transporter SLC30A10 may be explained by reduced thyroxine production. J Biol Chem 292: 16605-16615, 2017.
  10. Mukhopadhyay S*. Familial manganese-induced neurotoxicity due to mutations in SLC30A10 or SLC39A14. Neurotoxicology 64: 278-283, 2018.
  11. Hutchens S, Liu C, Jursa T, Shawlot W, Chaffee BK, Yin W, Gore AC, Aschner M, Smith DR, Mukhopadhyay S*. Deficiency in the manganese efflux transporter SLC30A10 induces severe hypothyroidism in mice. J Biol Chem 292: 9760-9773, 2017.
  12. Zogzas CE, Aschner M, Mukhopadhyay S*. Structural elements in the transmembrane and cytoplasmic domains of the metal transporter SLC30A10 are required for its manganese efflux activity. J Biol Chem 291: 15940-15957, 2016.
  13. Selyunin AS, Mukhopadhyay S*. A conserved structural motif mediates retrograde trafficking of Shiga toxin types 1 and 2. Traffic 16: 1270-1287, 2015.
  14. Leyva-Illades D, Chen P, Zogzas CE, Hutchens S, Mercado JM, Swaim CD, Morrisett RA, Bowman AB, Aschner M*, Mukhopadhyay S*. SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism causing mutations block its intracellular trafficking and efflux activity. J Neurosci 34: 14079-14095, 2014.
  15. Mukhopadhyay S, Linstedt AD. Retrograde trafficking of AB5 toxins: mechanisms to therapeutics. J Mol Med 91: 1131-1141, 2013.
  16. Mukhopadhyay S, Redler B, Linstedt AD. Shiga toxin-binding site for host cell receptor GPP130 reveals unexpected divergence in toxin-trafficking mechanisms. Mol Biol Cell 24: 2311-2318, 2013.
  17. Mukhopadhyay S, Linstedt AD. Manganese blocks intracellular trafficking of Shiga toxin and protects against Shiga toxicosis. Science 335: 332-335, 2012.
  1. Mukhopadhyay S, Linstedt AD. Identification of a gain-of-function mutation in a Golgi P-type ATPase that enhances Mn2+ efflux and protects against toxicity. Proc Natl Acad Sci USA 108: 858-863, 2011.
  2. Mukhopadhyay S, Bachert C, Smith DR, Linstedt AD. Manganese-induced trafficking and turnover of the cis-Golgi glycoprotein GPP130. Mol Biol Cell 21:1282-1292, 2010.

 

 

  1. Bruce A. Fowler Young Investigator Award, Society of Toxicology, 2019.
  2. Editor, Neurochem Res, 2019 onwards.
  3. Editorial Board Member, Neurotoxicology, 2019 onwards.
  4. NIH/NIEHS Extramural Paper of the Month (Taylor et al, J Biol Chem), March 2019.
  5. NIH/NIEHS Paper of the Year (Taylor et al, J Biol Chem), 2019.
  6. Highlight of career by NIH/NIEHS in “Stories of Success”, 2018.
  7. NIH/NIEHS “Outstanding New Environmental Scientist (ONES)” R01, 2016 – 2020.
  8. NIH/NIEHS K99/R00 “Pathway to Independence”, 2011 – 2018.
  9. Postdoctoral Fellowship, American Heart Association, 2011.
  10. Predoctoral Fellowship, American Heart Association, 2007 – 2008.
  11. Grant-in-Aid of Research, Sigma Xi, the Foundation for Scientific Research, 2007.
  12. Grant-in-Aid of Research, American Foundation for Aging Research, 2007.

 

  1. Fundamentals of fluorescence microscopy - Course director. This course provides a complete overview of fluoresence microscopy. Enrollment is limited to advanced graduate students. Students get a background in the theoretical principles of microscopy, including how different types of confocal microscopes function; hands-on experience in diverse microscopy techniques; and have the opportunity to meet with industrial faculty from leading microscope and camera manufactures such as Nikon and Andor.