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Department of Biology and Biochemistry

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Faculty Profile

Seema KhuranaSeema Khurana

Moores Professor
Department of Biology and Biochemistry
Research Division: Cell and Molecular Biology (Primary)

Office: Science & Research 2, 421E
Contact: skhurana@uh.edu - (713) 743-2705

ResearchGate Profile

Dr. Khurana has had a career spanning over three decades leading a federally funded research program studying the cell biology and physiology of the gastrointestinal tract. Additionally, research in her laboratory was supported by funding received from The American Digestive Health Foundation, The American Cancer Society and The American Heart Association. Her research program focuses on mucosal biology, the actin cytoskeleton, and gastrointestinal health and disease. Her laboratory has played a key role in the advancement of knowledge in the areas of intestinal injury-repair mechanisms in inflammatory bowel disease (IBD); therapeutic targeting of mucosal healing in IBD; epithelial-mesenchymal-transition and its contribution to intestinal injury-repair and metastatic colorectal carcinomas (CRCs); and the role of actin-regulatory proteins in maintaining epithelial homeostasis and as key drivers of gastrointestinal diseases like IBD and CRC. My laboratory has also contributed to structure-function studies identifying how cytoskeletal proteins like villin1, gelsolin, advillin, and fascin1 are themselves regulated and by identifying the molecular mechanisms of these proteins in IBD, CRC, and kidney disease, among others.

Ongoing research in her laboratory focuses on IBD and CRC with the goal to define how defects in epithelial cell-cell adhesions contribute to the etiology of both diseases. The maintenance of intestinal epithelial barrier function and the control of paracellular permeability is regulated by cell-cell adhesion structures called tight junctions. Defects in intestinal tight junctions and increased permeability of the gut barrier (often referred to as ‘leaky gut’) are linked to the initiation and progression of IBD. Notably, a growing body of evidence now links defects in intestinal tight junction permeability to neuroinflammation and the etiology of Parkinson’s disease and Alzheimer’s disease as well as to the pathogenesis of both type1 and type 2 diabetes. Ongoing studies in the laboratory are directed to identifying the role of the transcription factors, HNF4α/γ in the regulation of tight junction assembly and function and to defining how defects in tight junction associated gene transcription contribute to the initiation and progression of IBD. Additionally, by defining the underlying mechanism of tight junction defects in IBD, her laboratory also seeks to develop novel therapies for permeability healing in IBD. CRC is the third most prevalent malignant cancer and the second leading cause of cancer-related deaths worldwide. Serrated pathway CRCs comprise a third of all sporadic CRCs and they arise from neoplastic lesions with a saw tooth or serrated appearance and a mutation in the proto-oncogene Braf. Serrated CRCs are extremely aggressive, treatment refractory, and have the poorest outcome of all CRCs. Ongoing work in her laboratory shows that oncofetal actin cross-linking protein fascin1 plays a key role in serrated pathway colorectal carcinogenesis by remodeling another type of cell-cell adhesion structure called adherens junctions. Current research in her laboratory shows that by simply remodeling the mechanical force transduction at the adherens junctions, fascin1 can mechanoactivate WNT/β-catenin signaling, a key pathway linked to the initiation and progression of CRCs. By defining how fascin1 changes adherens junction mechanotransduction, the goal of her ongoing research is also to identify new therapeutic targets for the treatment of serrated pathway CRCs. IBD and CRC are multifactorial diseases characterized by heterogeneity, which affects both disease progression but more importantly treatment outcomes. Ongoing translational research in the laboratory is using high-throughput imaging and genetic profiling tools to capture IBD heterogeneity in patient samples. Additionally, by combining systems biology tools with advanced machine learning tools, current research effort in the laboratory is aimed at integration of multimodal patient sample data to better define the IBD sub-types. In addition to identifying the molecular characteristics of the IBD heterogeneous phenotypes, the laboratory hopes to use these unique phenotypes to perform drug library screen with the goal to lay the foundation of precision and personalized medicine in IBD. Other ongoing research in the laboratory is using a custom Cell Painting-based high-throughput quantitative imaging platform with single-cell resolution, to profile serrated pathway colorectal tumors to leverage phenotypic plasticity in CRCs for drug discovery and development for metastatic, treatment evasive, recurrent BrafV600E-mutated CRCs.

  • Esmaeilniakooshkghazi, A., Pham, E., George, S.P., Ahrorov, A., Villagomez, F.R., Byington, M., Mukhopadhyay, S., Patnaik, S., Bondesson, M., Conrad, J.C., Naik, M., Ravi, S., Tebbutt, N., Mooi, J., Reehorst, C.M., Mariadason, J.J., Khurana, S. (2023) In colon cancer cells fascin1 regulates adherens junction remodeling. FASEB J 37(3): e22786.
  • George, S.P., Esmaeilniakooshkghazi, A., Roy, S., Khurana, S. (2020) F-actin bundling sites are conserved in proteins with villin-type headpiece domains. Mol Biol Cell 31: 1857-1866.
  • Esmaeilniakooshkghazi, A., George, S.P., Biswas, R., Khurana, S. (2020) Mouse intestinal tuft cells express advillin but not villin. Sci Rep (Nature) 10: 8877.
  • Roy, S., Esmaeilniakooshkghazi, A., Patnaik, S., Wang, Y., George, S.P., Ahrorov, A., Hou, J.K. Herron, A.J. Sesaki, H., Khurana, S. (2018) Villin-1 and gelsolin regulate changes in actin dynamics that affect cell survival signaling pathways and intestinal inflammation. (2018) Gastroenterology 154: 1405-20.
  • Rao, J., Ashraf, S., Tan, W., van der Ven, A., Gee, H.Y., Braun, D.A., Feher, K., George, S.P., Esmaeilniakooshkghazi, A., Choi, W.I., Jobst-Schwan, T., Schneider, R., Schmidt, J.M., Widmeier, E., Warejko, J.K., Hermle, T., Schapiro, D., Lovric, S., Shril, S., Daga, A., Nayir, A., Shenoy, M., Tse, Y., Bald, M., Helmchen, U., Kari, J.A., Desoky, S.E., Soliman, N.A., Bagga, A., Mane, S., Jairajpuri, M.A., Lifton, R.P., Khurana, S., Martin, J.C., Hildebrandt, F. (2017) Advillin mutations delineate a comprehensive pathogenic pathway for steroid-resistant nephrotic syndrome. J Clin Invest 127: 4257-69.
  • Mikami, M., Zhang, Y., Danielsson, J., Joell, T., Yong, H.M., Twonsend, E., Khurana, S., S.S., Emala, C.W. (2017) Imapired relaxation of airway smooth muscle in mice lacking the cytoskeletal regulatory protein gelsolin. Am J. Respir Cell Mol Biol 10: 1165-75.
  • Patnaik S, George, S.P., Eric Pham, Mariadason, J.M., Khurana, S. (2016). By moonlighting in the nucleus villin regulates epithelial plasticity. Mol Biol Cell 27: 535-548.
  • Wang, Y., George, S.P., Roy, S., Pham, E., Khurana, S. (2016) Both the anti- and pro-apoptotic functions of villin regulate cell turnover and intestinal homeostasis. Nature Sci Rep 6: 35491 (1-9).
  • George, S.P., Chen, H., Conrad, J.C., Khurana, S. (2013). Regulation of directional cell migration by membrane-induced actin bundling. J Cell Sci 126: 312-326.
  • Wang, Y., Sudeep P. George, Kamalakkannan, S., Patnaik, S., Khurana, S. (2012) Actin reorganization as the molecular basis for the regulation of apoptosis in gastrointestinal epithelial cells. Cell Death and Differentiation 19: 1514-24.
  • Liu, W.M., Zhang, F., Moshiach, S., Zhou, B., Huang, C, Srinivasan, K., Khurana, S., Zheng, Y. Lahti, J.M., Zhang, X.A. (2012) Tetraspanin CD82 inhibits protrusion and retraction in cell movement by attenuating the plasma membrane-dependent actin organization. PLOS One 7(12): e51797
  • Khurana, S., George, S.P. (2011) The role of actin bundling proteins in the assembly of filopodia in epithelial cells. Cell Adhesion & Migration 5:1-12.
  • Tomar, A., George, S.P., Mathew, S., Khurana, S. (2009) Differential effects of lysophosphatidic acid and phosphatidylinositol 4,5-bisphosphate on actin dynamics by direct association with the actin-binding protein villin. J Biol Chem 284: 35278-82 (Accelerated Publication).
  • Mathew, S., George, S.P., Wang, Y., Siddiqui, M.R., Srinivasan, K., Tan, L., Khurana, S. (2008) Potential molecular mechanism for c-Src kinase mediated regulation of intestinal cell migration. J Biol Chem 283: 22709-22.
  • Khurana, S., George, S.P. (2008) Regulation of cell structure and function by actin-binding proteins: Villin’s perspective. FEBS Lett. In press, published Feb 26, 2008.
  • Wang, Y., Kamalakkannan, S., Siddiqui, M.R., George, S.P., Tomar, A., Khurana, S. (2008) A novel role for villin in intestinal epithelial cell survival and homeostasis. J Biol Chem 283: 9454-9464.
  • George, S.P., Wang, Y., Mathew, S., Kamalakkannan, S., Khurana, S. (2007) Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders. J Biol Chem 282: 26528-41.
  • Wang, Y., Tomar, A., George, S.P., Khurana, S. (2007) Obligatory role for phospholipase C-gamma 1 in villin-induced epithelial cell migration. Am J Physiol Cell Physiol 292: C1775-86.
  • Khurana, S., Tomar, A., George, S.P., Wang, Y., Siddiqui, M.R., Guo, H., Tigyi, G., Mathew, S. (2007) Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia. Exp Cell Res 314: 530-542.
  • Tomar, A., George, S., Kansal, P., Wang, Y., Khurana, S. (2006) Interaction of phospholipase C-γ1 with villin regulates epithelial cell migration. J Biol Chem 281, 31972-31986.
  • Khurana, S. (2006) Structure and Function of villin. In: Aspects of the cytoskeleton. Advances in Molecular and Cellular Biology, 37. Series Editor: E. Edward Bittar. Volume Editor: Seema Khurana. Elsevier Science.
  • Tomar, A., Wang, Y., Kumar, N., George, S., Ceacareanu, B., Hassid, A., Chapman, K.E., Aryal, A.M., Waters, C.M., Khurana, S. (2004) Regulation of cell motility by tyrosine phosphorylated villin. Mol Biol Cell 15, 4807-17.
  • Kumar, N., Tomar, A., Parrill, A.L., Khurana, S. (2004) Functional dissection and molecular characterization of calcium-sensitive actin-capping and actin-depolymerizing sites in villin. J Biol Chem 279, 45036-46.
  • Kumar, N., Khurana, S. (2004) Identification of a functional switch for actin severing by cytoskeletal proteins. J Biol Chem 279, 24915-18 (Accelerated Publication).
  • Kumar, N., Zhao, P., Tomar, A., Galea, C.A., Khurana, S. (2004) Association of villin with phosphatidylinositol 4,5-bisphosphate regulates the actin cytoskeleton J Biol Chem 279, 3096-3110.
  • Zhai, L., Kumar, N., Zhao, P., Panebra, A., Parrill, A., Khurana, S. (2002) Regulation of actin dynamics by tyrosine phosphorylation: Identification of tyrosine phosphorylation sites within the actin-severing domain of villin. Biochemistry 41, 11750-11760.
  • Zhai, L-W. Zhao, P., Panebra, A., Khurana, S. (2001) Tyrosine phosphorylation of villin regulates the organization of the actin cytoskeleton. J Biol Chem 276, 36163-67 (Accelerated Publication).
  • Panebra, A., Ma, S-X., Zhai, L-W., Wang, X-T., Rhee, S.G., Khurana, S. (2001) Regulation of Phospholipase C-γ1 by the actin regulatory protein villin. Am J Physiol Cell Physiol 281, C1046-58.
  • Khurana, S. Role of actin cytoskeleton in regulation of ion transport: Examples from epithelial cells. (2000) J Membrane Biol 178, 73-87.
  • Khurana, S., Arpin, M., Patterson, R., Donowitz, M. (1997) Ileal microvillar protein villin is tyrosine phosphorylated and associates with PLC-γ1. J Biol Chem 272, 30115-30121.
  • Khurana, S., Nath, S.K., Levine, S.A., Bowser, J.M., Tse, C.M., Cohen, M.E., Donowitz, M. (1996) Brush border phosphatidylinositol 3-kinase mediates epidermal growth factor stimulation of intestinal NaCl absorption and Na+/H+ exchange. J Biol Chem 271, 9919-9927.
  • Khurana, S., Kreydiyyeh, S. Aronzon, A., Hoogerwerf, W.A., Rhee, S.G., Donowitz, M., Cohen, M.E. (1996) Asymmetric signal transduction in polarized ileal Na+ absorbing cells: carbachol activates brush border but not basolateral membrane PI-PLC and translocates PLC-γ1 only to the brush border. Biochem J 313, 509-518.
  • Chatterjee, S., Ghosh, N., Khurana, S. (1991) Purification of uridine diphosphategalactose: glucosylceramide, β1-4 galactosyltransferase from human kidney. J Biol Chem 267, 7148-7153.

Selected Honors & Awards

  • 2024: John and Rebecca Moores Professor
  • 2020: 50 in 5 Award, University of Houston 2020
  • 2010-2012: Member College of CSR Reviewers (Jan 2010- July 2012), NIH
  • 1998-2002: American Digestive Health Foundation Industry Research Scholar Award 1998
  • 1998-2001: Council for Scientific and Industrial Research Fellowship, Government of India
  • 1989-1991: Indian Council of Medical Research Fellowship, Government of India
  • 1988: ESSA Scholarship, Ministry of Defense, Government of India
  • 1987: Dr. Ramji Omavati Gold Medal, Panjab University, India
  • 1987: Punjab University Medal, M.Sc. (Hons.), Biochemistry
  • 1985: Panjab University Students Council for Academic Achievements Award

Professional Affiliations

  • Member of the American Gastroenterological Association
  • American Gastroenterological Association Fellow.
  • Member of the Gastroenterological Research Association
  • Member of the American Physiological Society
  • Member of the Society of General Physiologists
  • Member of the American Cancer Society
  • Member of the American Society for Cell Biology

Selected Achievements

  • 2024: Reviewer, Veterans Affairs, Military Exposures Research Program (MERP).
  • 2006-Present: Reviewer, European Science Foundation.
  • 2022-Present: Reviewer, NCI, Clinical and Translational Cancer Research.
  • 2022-2024: Reviewer, Veterans Affairs, Biomedical Laboratory/Clinical Science Scientific Merit Review Board.
  • 2022-Present: Reviewer, Veterans Affairs Advisory Committee, Special Emphasis on Gulf War Research.
  • 2022-2023: Reviewer, NIDDK, Digestive and Nutrient Physiology and Diseases (DNPD).
  • 2022-Present: Reviewer, NIGMS, ZRG1 F05-D, Cell Biology, Developmental Biology and Bioengineering.
  • 2015-2021: Regular Member, NIDDK, Gastrointestinal Mucosal Pathobiology (GMPB now DHMI).
  • 2016-2022: Reviewer, NIH, National Center for Advancing Translational Sciences, Special Emphasis Panel.
  • 2018-2021: American Physiological Society, GI and Liver Trainee Symposium, Experimental Biology Meeting, Judge Poster Presentations.
  • 2015-2015: Reviewer, NIDDK, NIDD/DDN (Digestive Diseases and Nutrition) Fellowship Panel.
  • 2013-2015: Reviewer, NIGMS, Fellowship, Cell Biology, Developmental Biology and Bioengineering.
  • 2011-2015: Regular Member, NIDDK, Gastrointestinal Mucosal Pathobiology.
  • 2010-2012: Member, College of CSR Reviewers.
  • 2010-2010: Reviewer, NIGMS, Special Emphasis panel on new biomedical frontiers at the interface of life and physical sciences.
  • 2002-2009: NIDDK, Fellowship, Physiology and Pathobiology of Organ Systems.
  • 2008-2009: Reviewer, American Heart Association, Basic Cell, and Molecular Biology.
  • 2008-2010: Reviewer, Dutch Cancer Society, Amsterdam, Netherlands.
  • 2001-2010: Reviewer, Veterans Affairs, Merit Review Board.
  • 2008-2009: Member, American Heart Association, R2 Basic Cell, and Molecular Biology.
  • 2008-2008: Reviewer, Special Emphasis Panel, NIDDK, ZDK1, GRB-N.
  • 2008: Chair, American Gastroenterological Association, DDW Research Forum, Enterocyte Biology.
  • 2008: Chair, American Gastroenterological Association, DDW, Abstract Review Committee, Intestinal Injury and Repair.
  • 2007: Chair, American Gastroenterological Association, DDW Research Forum, Intestinal Absorption.
  • 2006-2009: Reviewer, Medical Research Council, U.K.
  • 2006-2010: Reviewer, National Medical Research Council, Ministry of Health, Government of Singapore.
  • 2006: Chair, American Gastroenterological Association, DDW, Abstract Review Committee, Intestinal Absorption.
  • 2005-2009: Member, American Gastroenterological Association, DDW, Abstract Review Committee.
  • 2005-2009: Regular Member, NIDDK, CIGP Study Section.
  • 2003-2009: Editorial Board, American Journal of Physiology – Gastrointestinal and Liver Physiology.
  • 2002-2008: Member, NIH, NRSA Fellowship Award.
  • 2001-2008: Reviewer, Veterans Affairs, Merit Review Board.
  • 1997-2003: Reviewer, NIDDK, General Medicine II Study Section.
  • 2012-2015: Vice-Chair, University Commission on Women, University of Houston.
  • 2012: Reviewer, Texas Medical Center Digestive Diseases (DDC) Pilot Program, Baylor College of Medicine, Houston, TX.
  • 2012-2016: Member T32 Postdoctoral Scientific Committee, Department of Gastroenterology, Baylor College of Medicine, Houston, TX.
  • 1999-2001: Consultant, Committee “New Dynamics” to promote gender equity and promote productivity by collegiality in the School of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.