Aron Parekh, Ph.D.
Assistant Professor of Otolaryngology
2220 Pierce Avenue
746A Preston Research Building
Nashville, TN 37232
Tumors are more rigid than surrounding normal tissue and experience increased tissue tension. The changes in the mechanical properties of tumors can drive cancer cell invasion. My laboratory is interested in understanding how mechanical forces regulate cancer cell phenotype.
Tumors are more rigid than surrounding normal tissue and experience increased tissue tension. The changes in the mechanical properties of tumors can drive cancer cell invasion. My laboratory is interested in understanding how mechanical forces regulate cancer cell phenotype. In particular, we are interested in how cancer cells sense these differences in mechanical properties and translate them to extracellular matrix degradation by invadopodia. Invadapodia facilitate extracellular matrix degradation which allows cancer cells to invade and metastasize. Therefore, our long term goal is to understand the biomechanical regulation of cancer cell invasion to identify targets to hinder cancer progression. We use a variety of in vitro, ex vivo, and computational techniques to understand how tissue mechanics regulates the invasive phenotype of cancer cells. These include microscopy (widefield, confocal, live cell), molecular and cellular techniques (RNAi, immunofluorescence, Westerns), synthetic and tissue-derived substrates (polyacrylamide gels, urinary bladder matrix), mechanical characterization of substrates (rheometry, atomic force microscopy), continuum mechanics (cellular traction force analyses), and development of novel assays and custom-made bioreactors to expose cancer cells to different mechanical environments.
- 1992-96, Pennsylvania State University, State College, PA; B.S., Chemical Engineering
- 1997-04, Pennsylvania State University, State College, PA; Ph.D., Chemical Engineering with Option in Biomolecular Transport Dynamics
- 2004-06, Postdoctoral Fellow, Children's Hospital of Pittsburgh, Pittsburgh, PA; Department of Pediatric Otolaryngology
- 2006-08, Postdoctoral Scholar, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering
- 2008-10, Research Fellow, Vanderbilt University Medical Center, Nashville, TN; Department of Cancer Biology
Proper cell and extracellular matrix (ECM) interactions are responsible for maintaining functional homeostasis in tissues and organs. Alterations in this reciprocal relationship following disease or injury are guided by changes in the local ECM mechanical environment, milieu of signaling molecules, and/or interactions with other cell types. These changes drive the ensuing disease state and tissue repair response by altering cellular phenotypes resulting in outcomes such as cancer cell invasion and pathological remodeling of healing wounds. In order to modulate these mechanobiological responses, a fundamental understanding of the biochemical and biophysical factors that influence these processes are required. These factors dictate cellular phenotypes and thus determine the manner in which cells further interact with their ECM microenvironment. Clinical modalities can be developed by identifying therapeutic targets that drive these pathological responses toward a more favorable outcome by interfering with these cell/ECM interactions. Therefore, our general research goal is to understand how mechanical forces drive pathologic cellular phenotypes in cancer and wound healing by utilizing biochemical and biomechanical approaches that include in vitro, ex vivo, in vivo, and in silico techniques and/or models.
- Jerrell RJ, Parekh A. Matrix rigidity differentially regulates invadopodia activity through ROCK1 and ROCK2. Biomaterials [print-electronic]. 2016 Apr; 84: 119-29. PMID: 26826790, PMCID: PMC4755854, PII: S0142-9612(16)00036-3, DOI: 10.1016/j.biomaterials.2016.01.028, ISSN: 1878-5905.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26826790.
- Parekh A, Weaver AM. Regulation of invadopodia by mechanical signaling. Exp. Cell Res [print-electronic]. 2015 Nov 11/4/2015; PMID: 26546985, PII: S0014-4827(15)30143-9, DOI: 10.1016/j.yexcr.2015.10.038, ISSN: 1090-2422.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26546985.
- Jerrell RJ, Parekh A. Polyacrylamide gels for invadopodia and traction force assays on cancer cells. J Vis Exp. 2015; (95): 52343. PMID: 25590238, PMCID: PMC4354498, DOI: 10.3791/52343, ISSN: 1940-087X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/25590238.
- Jerrell RJ, Parekh A. Cellular traction stresses mediate extracellular matrix degradation by invadopodia. Acta Biomater [print-electronic]. 2014 May; 10(5): 1886-96. PMID: 24412623, PMCID: PMC3976707, PII: S1742-7061(14)00002-6, DOI: 10.1016/j.actbio.2013.12.058, ISSN: 1878-7568.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/24412623.
- Weaver AM, Page JM, Guelcher SA, Parekh A. Synthetic and tissue-derived models for studying rigidity effects on invadopodia activity. Methods Mol. Biol. 2013; 1046: 171-89. PMID: 23868588, DOI: 10.1007/978-1-62703-538-5_10, ISSN: 1940-6029.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23868588.
- Heise RL, Parekh A, Joyce EM, Chancellor MB, Sacks MS. Strain history and TGF-ß1 induce urinary bladder wall smooth muscle remodeling and elastogenesis. Biomech Model Mechanobiol [print-electronic]. 2012 Jan; 11(1-2): 131-45. PMID: 21384200, PMCID: PMC3155650, DOI: 10.1007/s10237-011-0298-y, ISSN: 1617-7940.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21384200.
- Parekh A, Ruppender NS, Branch KM, Sewell-Loftin MK, Lin J, Boyer PD, Candiello JE, Merryman WD, Guelcher SA, Weaver AM. Sensing and modulation of invadopodia across a wide range of rigidities. Biophys. J. 2011 Feb 2/2/2011; 100(3): 573-82. PMID: 21281571, PMCID: PMC3030182, PII: S0006-3495(11)00010-5, DOI: 10.1016/j.bpj.2010.12.3733, ISSN: 1542-0086.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/21281571.
- Parekh A, Cigan AD, Wognum S, Heise RL, Chancellor MB, Sacks MS. Ex vivo deformations of the urinary bladder wall during whole bladder filling: contributions of extracellular matrix and smooth muscle. J Biomech [print-electronic]. 2010 Jun 6/18/2010; 43(9): 1708-16. PMID: 20398903, PII: S0021-9290(10)00143-0, DOI: 10.1016/j.jbiomech.2010.02.034, ISSN: 1873-2380.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/20398903.
- Heise RL, Ivanova J, Parekh A, Sacks MS. Generating elastin-rich small intestinal submucosa-based smooth muscle constructs utilizing exogenous growth factors and cyclic mechanical stimulation. Tissue Eng Part A. 2009 Dec; 15(12): 3951-60. PMID: 19569874, PMCID: PMC2792073, DOI: 10.1089/ten.TEA.2009.0044, ISSN: 1937-335X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19569874.
- Parekh A, Long RA, Chancellor MB, Sacks MS. Assessing the effects of transforming growth factor-beta1 on bladder smooth muscle cell phenotype. II. Modulation of collagen organization. J. Urol [print-electronic]. 2009 Sep; 182(3): 1216-21. PMID: 19625051, PII: S0022-5347(09)01141-0, DOI: 10.1016/j.juro.2009.05.004, ISSN: 1527-3792.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19625051.
- Parekh A, Long RA, Iannone EC, Chancellor MB, Sacks MS. Assessing the effects of transforming growth factor-beta1 on bladder smooth muscle cell phenotype. I. Modulation of in vitro contractility. J. Urol [print-electronic]. 2009 Sep; 182(3): 1210-5. PMID: 19625042, PII: S0022-5347(09)01139-2, DOI: 10.1016/j.juro.2009.05.002, ISSN: 1527-3792.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19625042.
- Parekh A, Weaver AM. Regulation of cancer invasiveness by the physical extracellular matrix environment. Cell Adh Migr [print-electronic]. 2009 Jul; 3(3): 288-92. PMID: 19458499, PMCID: PMC2712813, PII: 8888, ISSN: 1933-6926.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19458499.
- Parekh A, Mantle B, Banks J, Swarts JD, Badylak SF, Dohar JE, Hebda PA. Repair of the tympanic membrane with urinary bladder matrix. Laryngoscope. 2009 Jun; 119(6): 1206-13. PMID: 19358244, PMCID: PMC3003594, DOI: 10.1002/lary.20233, ISSN: 1531-4995.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19358244.
- Parekh A, Sandulache VC, Singh T, Cetin S, Sacks MS, Dohar JE, Hebda PA. Prostaglandin E2 differentially regulates contraction and structural reorganization of anchored collagen gels by human adult and fetal dermal fibroblasts. Wound Repair Regen. 2009 Jan; 17(1): 88-98. PMID: 19152655, PMCID: PMC3000117, PII: WRR445, DOI: 10.1111/j.1524-475X.2008.00445.x, ISSN: 1524-475X.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19152655.
- Alexander NR, Branch KM, Parekh A, Clark ES, Iwueke IC, Guelcher SA, Weaver AM. Extracellular matrix rigidity promotes invadopodia activity. Curr. Biol [print-electronic]. 2008 Sep 9/9/2008; 18(17): 1295-9. PMID: 18718759, PMCID: PMC2555969, PII: S0960-9822(08)01035-X, DOI: 10.1016/j.cub.2008.07.090, ISSN: 0960-9822.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/18718759.
- Sandulache VC, Parekh A, Dohar JE, Hebda PA. Fetal dermal fibroblasts retain a hyperactive migratory and contractile phenotype under 2-and 3-dimensional constraints compared to normal adult fibroblasts. Tissue Eng. 2007 Nov; 13(11): 2791-801. PMID: 17764403, DOI: 10.1089/ten.2006.0412, ISSN: 1076-3279.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17764403.
- Merryman WD, Liao J, Parekh A, Candiello JE, Lin H, Sacks MS. Differences in tissue-remodeling potential of aortic and pulmonary heart valve interstitial cells. Tissue Eng. 2007 Sep; 13(9): 2281-9. PMID: 17596117, DOI: 10.1089/ten.2006.0324, ISSN: 1076-3279.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17596117.
- Parekh A, Velegol D. Collagen gel anisotropy measured by 2-D laser trap microrheometry. Ann Biomed Eng [print-electronic]. 2007 Jul; 35(7): 1231-46. PMID: 17380393, DOI: 10.1007/s10439-007-9273-2, ISSN: 0090-6964.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17380393.
- Parekh A, Sandulache VC, Lieb AS, Dohar JE, Hebda PA. Differential regulation of free-floating collagen gel contraction by human fetal and adult dermal fibroblasts in response to prostaglandin E2 mediated by an EP2/cAMP-dependent mechanism. Wound Repair Regen. 2007 May; 15(3): 390-8. PMID: 17537126, PII: WRR241, DOI: 10.1111/j.1524-475X.2007.00241.x, ISSN: 1067-1927.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17537126.
- Sandulache VC, Parekh A, Li-Korotky H, Dohar JE, Hebda PA. Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-beta1-induced collagen synthesis. Wound Repair Regen. 2007 Jan; 15(1): 122-33. PMID: 17244328, PII: WRR193, DOI: 10.1111/j.1524-475X.2006.00193.x, ISSN: 1067-1927.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17244328.
- Sandulache VC, Parekh A, Li-Korotky HS, Dohar JE, Hebda PA. Prostaglandin E2 differentially modulates human fetal and adult dermal fibroblast migration and contraction: implication for wound healing. Wound Repair Regen. 2006 Sep; 14(5): 633-43. PMID: 17014677, PII: WRR156, DOI: 10.1111/j.1743-6109.2006.00156.x, ISSN: 1067-1927.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/17014677.