Charles K. Thodeti, Ph.D.
Assistant Professor of Vascular Biology
Department of Integrative Medical Sciences
College of Medicine
Ph.D., Zoology (Physiology and Biochemistry Concentration), S. V. University, Tirupati, India - 1994
M.S., Zoology (Reproductive Physiology Specialization), S. V. University, Tirupati, India - 1987
B.S., Botany/Chemistry majors, S. V. University, Tirupati, India - 1985
Assistant Professor of Vascular Biology, Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio - 2009-Present
Instructor/Staff Scientist, Harvard Medical School/Children's Hospital, Boston, Mass. - 2004-2009
Research Associate Professor, University of Copenhagen, Denmark - 2000-2004
Post-Doctoral Fellow, Lund University, Sweden - 1997-2000
Research Associate, University of Hyderabad, Hyderabad, India - 1995-1996
North American Vascular Biology Organization
American Heart Association
American Physiology Society
TRPV4, Angiogenesis and Cancer: Don Ingber and Charles Thodeti (NEOMED with Harvard Med Sch/Children’s Hosp Boston).
Editorial Board member of Journal of Cancer Science & Therapy
1. Circulation Research
5. J Mol Cell Cardiol.
6. Am J Physiol Heart Circ. Physiol
7. Basic Research in Cardiology
8. J Cell Physiol.
9. PLOS One
10. Cell Calcium
11. Cell Mol Bioengineering
12. Integrative Biology
13. Am J Physiol Reg Physiol
14. Scientific Reports
16. J Appl. Physiol.
AHA Scientific Sessions Abstracts grader -2011, 2012, 2013, 2014.
AHA Scientific Sessions Moderator, Sessions builder and Chair for on Angiogenesis (2012).
International: Yorkshire Cancer Research, UK.
National: Study section reviewer - OCAST (Oklahoma Center for the Advancement of Science & Technology) 2013, 2014
AHA-Basic Cell MSO 3- April, 2014
AHA-Basic Cell IRG- October, 2014
NEOMED: Summer Research Fellowships-2014
AHA-Basic Cell MSO 2-April, 2015
Anna University, India
Acharya Nagarjuna University, India
1. Principal Investigator: AHA grant-In-Aid: Mechanical control of endothelial cell function during angiogenesis. 2014-2016.
2. Principal Investigator (co-PI): NIH-R15: Post-infarction repair of the diabetic myocardium.2012-15.
3. Principal Investigator: NEOMED start-up funds
1. Principal Investigator (co-PI): NEOUCOM-Research Incentive grant: Post-infarction repair of the diabetic myocardium using myofibroblasts.2010.
2. Principal Investigator (MPI): Akron Children’s Hospital Foundation: Fabricating a biopolymer construct to optimize chondrocyte growth.” 2009-2010.
3. Principal Investigator: AHA- Scientist Development Grant: Mechanical Control of Integrin activation in Capillary Endothelial Cells 2006-2009 Jun.
4. Co- Principal Investigator: Dansk Kræftforsknings Fond (Danish Cancer Research Fund), 2004.
1) Principal Investigator: NIH R01: Mechanotransduction in myocardial adaptations to ischemia. Score: 18 percentile (A1).
2) Principal Investigator: NIH R01: Role of mechanosensitive ion channels in angiogenesis: Score: 16 percentile (A1).
Mechanical Control of Endothelial Cell Function, Angiogenesis and Stem Cell Differentiation
Cells within all living tissues encounter mechanical forces continuously within a changing dynamic environment, and increasing evidence suggests that mechanical forces regulate cell growth, differentiation, motility, protein synthesis and gene expression. Importantly, mechanical forces are critical regulators of cardiovascular physiology and pathophysiology. Therefore, understanding how cells sense and convert mechanical signals into biochemical signals, mechanotransduction, could offer novel therapeutic targets for treatment of various cardiovascular diseases and in vitro engineering of organs and tissues such as blood vessels. The long-term goal of my research is to work at the interface between soluble and solid state biochemistry using multidisciplinary approaches to investigate the biophysical, biomechanical and biomechanical mechanisms regulating endothelial cell function and angiogenesis and utilize the knowledge to develop effective vascular normalization therapies for cardiovascular abnormalities such as atherosclerosis, hypertension, diabetes and cancer.
Currently, my laboratory is focused on understanding the role of mechanosensitive TRPV4 ion channels in the regulation of:
- Tumor angiogenesis: Tumor vessels are characterized by abnormal morphology and patterning that cause vascular hyperpermeability and inefficient delivery of anti-cancer agents. We recently demonstrated that these vessel malformations may arise from aberrant Rho-mediated mechanosensing exhibited by tumor endothelial cells in response to mechanical strain. We also found that TRPV4 channels are required for endothelial cell reorientation in response to mechanical force. Therefore, we are investigating the role of TRPV4 channels and dependent signaling mechanisms in the regulation of tumor endothelial cell mechanosensitivity in order to identify novel targets that can be potentially used to normalize abnormal tumor vasculature and improve delivery of chemotherapeutic drugs in vivo.
- Stem cell differentiation into bone and cartilage: Mechanical forces are critical determinants of tissue morphogenesis including bone which is continuously exposed to mechanical forces. Indeed, local micromechanical forces have been shown to regulate human mesenchymal stem cell commitment to bone forming osteoblast like cells. Our focus in this project is to elucidate the biomechanical mechanisms that regulate stem cell differentiation in to bone and cartilage. To this end, we are collaborating with the Departments of Polymer Engineering, University of Akron and Plastic Surgery, Akron Children's Hospital to develop tissue engineering scaffolds that are mechanically osteo-inductive for bone regeneration therapy.
Peer Reviewed Publications (in reverse chronological order):
Adapala R, Thoppil R, Ghosh K, Cappelli H, Dudley AC, Paruchuri S, Keshamouni V, Klagsbrun M, Meszaros JG, Chilian W, Ingber D, and Thodeti CK*. (2014) Activation of mechanosensitive ion channel TRPV4 normalizes tumor vasculature and improves cancer therapy. Oncogene. (In Press)
Rahaman SO, Grove LM, Paruchuri S, Southern BD, Abraham S, Niese KA, Scheraga RG, Ghosh S, Thodeti CK, Zhang DX, Moran MM, Schilling WP, Tschumperlin DJ, Olman MA. (2014). TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice. J Clin Invest. 124(12):5225-38.
Al-Azzam N, Kondeti V, Duah E, Gombedza F, Thodeti CK, and Paruchurri S. Modulation of mast cell proliferative and inflammatory responses by Leukotriene D4 and Stem Cell Factor interactions. J. Cell Physiol. 2014, Aug. 27. doi: 10.1002/jcp.24777. [Epub ahead of print]
Shamhart PE, Luther DJ, Adapala RK, Bryant JE, Peterson, KA, Meszaros JG, and Thodeti CK*. (2014) Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts. Canadian J. Physiol. Pharmacol. 92(7):598-604.
Duah E, Adapala RK, Al-Azzam N, Kondeti V, Gombedza F, Thodeti CK, and Paruchuri S. (2013) Cysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT2 and SysLT1 receptors. Sci Rep. (Nature Publishing Group) 3:3274.
Luther DJ, Thodeti CK, and Meszaros JG. (2013) Injury models to study cardiac remodeling in the mouse: Myocardial infarction and ischemia-reperfusion. Methods Mol Biol. 1037:325-42.
Kondeti V, Duah E, Al-Azzam N, Thodeti CK, Boyce JA, and Paruchuri S. (2013) Differential regulation of cysteinyl leukotriene receptor signaling by protein kinase C in human mast cells. PLOS One. 8(8):e71536.
Thodeti CK, Paruchuri S, and Meszaros JG. (2013) A TRP to cardiac fibroblast differentiation. Channels.7:211-214.
Adapala RK, Thoppil R, Luther DJ, Sailaja P, Meszaros JG, Chilian WM, and Thodeti CK*. (2012) TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals. J. Mol. Cell. Cardiol. 54:45-52.
Jolanta MK, Carl S, Thodeti CK, Adapala RK, Ananth M, Alamgir K, (2012) Engineering 2.5D Constructs for Characterizing Phase Separated Polymer Blend Surface Morphology in Tissue Engineering Scaffolds. J. Biomed. mat. Res.: Part A doi:10.1002/jmb.a.34439.
Jones TJ, Adapala RK, Geldenhuys WJ, Bursley C, Aboualaiwi WA, Nauli SM, Thodeti CK. Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization. J Cell Physiol. 2011 Feb 24. doi: 10.1002/jcp.22704. [Epub ahead of print]
Luther DJ, Thodeti CK, Shamhart PE, Adapala RK, Hodnichak C, Weihrauch D, Bonaldo P, Chilian WM, and Meszaros JG. Absence of type VI collagen paradoxically improves cardiac function, structure, and remodeling after myocardial infarction. Circ. Res. 2012, March 16;110(6):851-6. (Cover Page)
Sero JE, Thodeti CK, Mammoto A, Bakal C, Thomas S, and Ingber DE. (2012) Paxillin mediates sensing of physical cues and regulates directional cell motility by controlling lamellipodia positioning. PLoS One 6(12):e28203.
Guarini G, Ohanyan V, Kmetz JG, Dellostritto D, Thoppil R, Thodeti CK, Meszaros JG, Damron DS, and Bratz I. (2012) Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: Role nitric oxide and BK channels. Am J Physiol Heart Circ Physiol. 303(2):H216-23.
Chavez RJ, Haney RM, Cuadra RH, Ganguly R, Adapala RK, Thodeti CK, and Raman P. (2012) Upregulation of Thrombospondin-1 Expression by Leptin in Vascular Smooth Muscle Cells via JAK2 and MAPK-dependent pathways. Am J Physiol Cell Physiol. 303(2):C179-91.
Ohanyan VA, Guarini G, Thodeti CK, Talasila PK, Raman P, Haney RM, Meszaros JG, Damron DS, and Bratz I. Endothelin-mediated in vivo pressor responses following TRPV1 activation. Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H1135-42. Epub 2011 Jun 24.
Adapala RK, Talasila PK, Bratz IN, Zhang DX, Suzuki M, Meszaros JG, Thodeti CK. PKCα mediates acetylcholine-induced activation of TRPV4-dependent calcium influx in endothelial cells. Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H757-65. Epub 2011 Jun 24.
Matthews BD, Thodeti CK, Tytell JD, Mammoto A, Overby DR, Ingber DE. Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins. Integr Biol (Camb). 2010 Sep;2(9):435-42. Epub 2010 Aug 20.
Chancellor TJ, Lee J, Thodeti CK, Lele T. Actomyosin tension exerted on the nucleus through nesprin-1 connections influences endothelial cell adhesion, migration, and cyclic strain-induced reorientation. Biophys J. 2010 Jul 7;99(1):115-23. Erratum in: Biophys J. 2010 Aug 9;99(4):1329.
Thodeti, C.K., Matthews, B., Ravi, A., Mamotto, A., Ghosh, K., and Bracha, A., Ingber, D.E. (2009) TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin to integrin signaling. Circ. Res. 104:1123-1130.
Alenghat FJ, Tytell J, Thodeti CK, Derrien A, and Ingber DE. (2009) Mechanical control of cAMP signaling through integrin-dependent activation of heterotrimeric Gαs protein in focal adhesions. J. Cell. Biochem. 106:529-38.
Ghosh, K., Thodeti, C.K., Dudley, A.C., Mammoto, A., Klagsbrun, M., and Ingber, D.E. ( 2008) Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro. Proc. Natl. Acad. Sci. USA 105: 11305-10.
Lele, T*., Thodeti, C.K*., Pendse, J., and Ingber, D.E. (2008) Investigating complexity of protein-protein interactions in focal adhesions. Biochem. Biophys. Res. Commun. 369:929-34
*Shared first author.
Xia N, Thodeti CK, Hunt TP, Xu Q, Ho M, Whitesides GM, Westervelt R, and Ingber DE. (2008) Directional control of cell motility through focal adhesion positioning and spatial control of Rac activation. FASEB J. 22: 1649-59.
Lele T, Thodeti CK, and Ingber DE. (2006) Force meets chemistry: analysis of mechanochemical conversion in focal adhesions using fluorescence recovery after photobleaching. J.Cell.Biochem. 97:1175-83. (Cover Page).
Thodeti CK, Frohlich C, Nielsen CK, Takada Y, Fassler R, Albrechtsen R, and Wewer UM. (2005) ADAM12-mediated focal adhesion formation is differently regulated by β1 and β3 integrins. FEBS Lett. 579: 5589-95.
Thodeti CK, Frohlich C, Nielsen CK, Holck P, Sundberg C, Kveiborg M, Mahalingam Y, Albrechtsen R, Couchman JR, and Wewer UM. (2005) Hierarchy of ADAM12 binding to integrins in tumor cells. Exp Cell Res. 309:438-50.
Sundberg C*, Thodeti CK*, Kvieborg M, Larsson C, Parker P, Albrechtsen R, and Wewer U,M. (2004) Regulation of ADAM12 cell-surface expression by protein kinase C epsilon. J. Biol.Chem. 279:51601-11.
*Shared first author
Thodeti CK, Albrechtsen R, Grauslund M, Asmar M, Larsson C, Takada Y, Mercurio A, Couchman JR, and Wewer U.M. (2003) ADAM12/syndecan-4 signaling promotes β1integrin-dependent cell spreading through PKCα and Rho. J. Biol.Chem. 278:9576-9584.
Kawaguchi N, Sundberg C, Kveiborg M, Moghadaszadeh B, Asmar M, Dietrich N, Thodeti CK, Nielsen FC, Moller P, Mercurio AM, Albrechtsen R, and Wewer U.M.(2003) ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function. J.Cell Sci. 116: 3893-904.
Thodeti CK, Massoumi R, Bindslev L, and Sjolander A. (2002) Leukotriene D4 induces association of active RhoA with phospholipase C-g1 in intestinal epithelial cells. Biochem. J. 365:157-163.
Thodeti CK, and Sjölander A. (2002) Leukotriene D4-induced calcium signalling in human intestinal epithelial cells. Adv. Exp. Med. Biol. 507: 187-191.
Thodeti, C.K., Nielsen, C.K., Larsson, C., and Sjölander, A. (2001) The epsilon isoform of protein kinase C is involved in the regulation of the LTD4-induced calcium signal in human intestinal epithelial cells. Exp.Cell.Res. 262: 95-103.
Thodeti CK, Adolfsson J, Juhas M, and Sjölander A. (2000) Leukotriene D4 triggers an association between Gβγ subunits and phospholipase C-γ1 in intestinal epithelial cells. J.Biol.Chem. 275: 9849-9853.
Srinivasa Reddy P, Charles Kumar T, Narasa Reddy M, Sarada Ch, and Reddanna P. (2000) Differential formation of octadecadienoic acid and octadecatrienoic acid products in control and injured/infected potato tubers. Biochim. Biophys.Acta 1483: 294-300.
Anuradha D, Reddy KV, Charles Kumar T, Neeraja S, Reddy PR, and Reddanna P. (2000) Purification and characterization of rat testicular glutathione S-transferases: role in the synthesis of eicosanoids. Asian J.Androl. 2 :277-82.