Dr. Srikrishna is studying the role of damage associated molecular patterns (DAMP) in mediating inflammation and cancers.
Dr. Srikrishna earned her Masters and Ph.D. from the University of Madras, India.
Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells.
Sinha P, Okoro C, Foell D, Freeze HH, Ostrand-Rosenberg S, Srikrishna G
J Immunol. 2008 Oct 1;181(7):4666-75
RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis.
Turovskaya O, Foell D, Sinha P, Vogl T, Newlin R, Nayak J, Nguyen M, Olsson A, Nawroth PP, Bierhaus A, Varki N, Kronenberg M, Freeze HH, Srikrishna G
Carcinogenesis. 2008 Oct;29(10):2035-43
Carboxylated glycans mediate colitis through activation of NF-kappa B.
Srikrishna G, Turovskaya O, Shaikh R, Newlin R, Foell D, Murch S, Kronenberg M, Freeze HH
J Immunol. 2005 Oct 15;175(8):5412-22
Novel carboxylated N-glycans contain oligosaccharide-linked glutamic acid.
Srikrishna G, Brive L, Freeze HH
Biochem Biophys Res Commun. 2005 Jul 15;332(4):1020-7
N -Glycans on the receptor for advanced glycation end products influence amphoterin binding and neurite outgrowth.
Srikrishna G, Huttunen HJ, Johansson L, Weigle B, Yamaguchi Y, Rauvala H, Freeze HH
J Neurochem. 2002 Mar;80(6):998-1008
Two proteins modulating transendothelial migration of leukocytes recognize novel carboxylated glycans on endothelial cells.
Srikrishna G, Panneerselvam K, Westphal V, Abraham V, Varki A, Freeze HH
J Immunol. 2001 Apr 1;166(7):4678-88
A novel anionic modification of N-glycans on mammalian endothelial cells is recognized by activated neutrophils and modulates acute inflammatory responses.
Srikrishna G, Toomre DK, Manzi A, Panneerselvam K, Freeze HH, Varki A, Varki NM
J Immunol. 2001 Jan 1;166(1):624-32
Reduced heparan sulfate accumulation in enterocytes contributes to protein-losing enteropathy in a congenital disorder of glycosylation.
Westphal V, Murch S, Kim S, Srikrishna G, Winchester B, Day R, Freeze HH
Am J Pathol. 2000 Dec;157(6):1917-25
Dolichol phosphate mannose synthase (DPM1) mutations define congenital disorder of glycosylation Ie (CDG-Ie)
Kim S, Westphal V, Srikrishna G, Mehta DP, Peterson S, Filiano J, Karnes PS, Patterson MC, Freeze HH
J Clin Invest. 2000 Jan;105(2):191-8
Correction of leukocyte adhesion deficiency type II with oral fucose.
Marquardt T, Lühn K, Srikrishna G, Freeze HH, Harms E, Vestweber D
Blood. 1999 Dec 15;94(12):3976-85
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Pro-inflammatory S100A12 can Activate Human Monocytes via Toll-like Receptor 4.
Foell D, Wittkowski H, Kessel C, Lüken A, Weinhage T, Varga G, Vogl T, Wirth T, Viemann D, Björk P, van Zoelen MA, Gohar F, Srikrishna G, Kraft M, Roth J
Am J Respir Crit Care Med. 2013 Apr 23;
Geetha Srikrishna's Research Focus
Crohn’s Disease (Colitis), Cancer
Dr. Srikrishna is studying the role of DAMP molecules and their carbohydrate recognition epitopes in mediating mucosal inflammation and inflammation-based cancers. She found that novel anionic glycans, referred to as carboxylated glycans, which have restricted expression on human and mouse cells of the myeloid lineage, bind damage associated molecular patterns HMGB1 and S100 proteins, and mediate inflammation and promote carcinogenesis.
Geetha Srikrishna's Research Report
Dr. Srikrishna’s work through the last several years has shown that S100A8 and S100A9, well-known pro-inflammatory DAMP molecules that bind novel carboxylated glycans expressed on RAGE and other cell surface glycoproteins, have multiple roles in promoting malignancy in the tumor microenvironment.
1) promoting accumulation of myeloid-derived suppressor cells (MDSC) in tumors,
2) activation of signaling pathways in tumor cells leading to expression of several pro-tumorigenic proteins, and
3) promotion of pre-metastatic changes in distal organs in response to primary tumors
An antibody generated against carboxylated-glycans, expressed on RAGE and other cell surface glycoproteins, blocks the onset of colitis and colitis-associated colon carcinogenesis in mice, and accumulation of MDSC in mouse models of tumors. The glycans and the DAMP molecules that bind to them therefore provide potential targets for therapeutic interference in inflammatory disorders and tumors.
About Geetha Srikrishna
Dr. Srikrishna earned her Masters and Ph.D. from the University of Madras, India under the Faculty of Medicine while training in human anatomy, physiology, endocrinology and practicing clinical laboratory medicine at the Christian Medical College and Hospital, Vellore, India. She joined Dr. Hudson Freeze’s laboratory at Sanford-Burnham Medical Research Institute as a postdoctoral research associate in 1994, becoming a Staff Scientist in 2002 and Research Assistant Professor in 2006.