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Integrative Physiology & Pharmacology Ph.D. Program at Wake Forest University


Wake Forest University Graduate School » Integrative Physiology & Pharmacology Ph.D. Program

Thomas Smith, Ph.D.

Thomas Smith, Ph.D.
Research in our laboratory covers a wide range of topics applicable to Neuroscience. Current research encompasses techniques for optimizing outcomes of peripheral nerve repair as well as studies of the pathology of muscle degeneration following peripheral nerve injury or long-term neuromuscular blockade. In addition, ongoing studies investigate the regulation of the thermoregulatory microvasculature of the digits through autonomic control of this vasculature in normal and disease conditions. From a broader perspective, our laboratory also has an interest in the autonomic control of the cardiovascular system and integration of systemic and microvascular control. Our laboratory also trains Orthopaedic Residents in research techniques applicable a career in academic Orthopaedic Surgery. These residents are engaged in clinically relevant research and offer an opportunity to collaborate with academic physicians to better understand the perspective of our clinical colleagues. Our laboratory also teaches microsurgical technique and a variety of animal models are available for integrative physiological studies.

 

Krishnan B, Smith TL, Dubey P, Zapadka ME, Torti FM, Willingham MC, Tallant EA, Gallagher PE. Angiotensin-(1-7) attenuates metastatic prostate cancer and reduces osteoclastogenesis. Prostate. 2013;73(1):71-82.

 

de Guzman RC, Saul JM, Ellenburg MD, Merrill MR, Coan HB, Smith TL, Van Dyke ME. Bone regeneration with BMP-2 delivered from keratose scaffolds. Biomaterials. 2013;34(6):1644-1656.

 

 

Langfitt M, Webb LX, Onwuchuruba C, Callahan M, Smith TL. Microvascular effects of subatmospheric pressure in striated muscle. J Reconstr Microsurg. 2013;29(2):117-124.

 

Plate JF, Wiggins WF, Haubruck P, Scott AT, Smith TL, Saul KR, Mannava S.Normal aging alters in vivo passive biomechanical response of the rat gastrocnemius-Achilles muscle-tendon unit. J Biomech. 2013;46(3):450-455.

 

Plate JF, Haubruck P, Walters J, Mannava S, Smith BP, Smith TL, Tuohy CJ.Rotator cuff injuries in professional and recreational athletes. J Surg Orthop Adv. 2013;22(2):134-142.

 

Pace LA, Plate JF, Smith TL, Van Dyke ME. The effect of human hair keratin hydrogel on early cellular response to sciatic nerve injury in a rat model. Biomaterials. 2013;34(24):5907-5914.

 

Mannava S, Plate JF, Tuohy CJ, Seyler TM, Whitlock PW, Curl WW, Smith TL, Saul KR. The science of rotator cuff tears: translating animal models to clinical recommendations using simulation analysis. Knee Surg Traumatol Arthrosc. 2013;21(7):1610-1619.

 

Forrest LM, Lough CM, Chung S, Boudyguina EY, Gebre AK, Smith TL, Colvin PL, Parks JS. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice. Nutrients. 2013;5(7):2629-2645.

 

Stone AV, Koman LA, Callahan MF, Eckman DM, Smith BP, Plate JF, Smith TL. The effect of botulinum neurotoxin-A on blood flow in rats: a potential mechanism for treatment of Raynaud phenomenon. J Hand Surg [Am]. 2012;37(4):795-802.

 

Rong S, Cao Q, Liu M, Seo J, Jia L, Boudyguina E, Gebre AK, Colvin PL, Smith TL, Murphy RC, Mishra N, Parks JS. Macrophage 12/15 lipoxygenase expression increases plasma and hepatic lipid levels and exacerbates atherosclerosis. J Lipid Res. 2012;53(4):686-695.

 

Orlando G, Wood KJ, De Coppi P, Baptista PM, Binder KW, Bitar KN, Breuer C, Burnett L, Christ G, Farney A, Figliuzzi M, Holmes JH IV, Koch K, Macchiarini P, Mirmalek Sani S-H, Opara E, Remuzzi A, Rogers J, Saul JM, Seliktar D,.Regenerative medicine as applied to general surgery. Ann Surg. 2012;255(5):867-880.

 

Moran EC, Raghunathan S, Evans DW, Vavalle NA, Sparks JL, Leroith T, Smith TL.Porohyperviscoelastic model simultaneously predicts parenchymal fluid pressure and reaction force in perfused liver. J Biomech Eng. 2012;134(9):091002.

 

Haubruck P, Mannava S, Plate JF, Callahan MF, Wiggins WF, Schmidmaier G, Tuohy CJ, Saul KR, Smith TL. Botulinum neurotoxin A injections influence stretching of the gastrocnemius muscle-tendon unit in an animal model. Toxins. 2012;4(8):605-619.

 

Whitlock PW, Seyler TM, Parks GD, Ornelles DA, Smith TL, Van Dyke ME, Poehling GG. A novel process for optimizing musculoskeletal allograft tissue to improve safety, ultrastructural properties, and cell infiltration. J Bone Joint Surg Am. 2012;94(16):1458-1467.

 

Nunez FA, Kislukin V, Smith TL, Callahan MF, Burnett L, VanDyke ME.Hemodynamic response after hypovolemic shock and resuscitation with low-volume 6% hetastarch (HS) and high-volume lactated Ringer's (LR) solution [abstract]. FASEB J. 2012;26(Meeting Abstracts Suppl):1132.8.

 

Carver KA, Smith TL, Gallagher PE, Tallant EA. Vascular remodeling by angiotensin peptide hormones alters reactivity of the microcirculation [abstract]. Hypertension. 2012;60(3 Suppl):530.

 

Delo DM, Guan X, Wang Z, Groban L, Callahan M, Smith T, Sane DC, Payne RM, Atala A, Soker S. Calcification after myocardial infarction is independent of amniotic fluid stem cell injection. Cardiovasc Pathol. 2011;20(2):e69-e78.

 

Mannava S, Callahan MF, Trach SM, Wiggins WF, Smith BP, Koman LA, Smith TL, Tuohy CJ. Chemical denervation with botulinum neurotoxin a improves the surgical manipulation of the muscle-tendon unit: an experimental study in an animal model. J Hand Surg [Am]. 2011;36(2):222-231.

 

Hill PS, Apel PJ, Barnwell J, Smith T, Koman LA, Atala A, Van Dyke M. Repair of peripheral nerve defects in rabbits using keratin hydrogel scaffolds. Tissue Eng Part A. 2011;17(11-12):1499-1505.

 

Mannava S, Wiggins WF, Saul KR, Stitzel JD, Smith BP, Koman LA, Smith TL, Tuohy CJ. Contributions of neural tone to in vivo passive muscle-tendon unit biomechanical properties in a rat rotator cuff animal model. Ann Biomed Eng. 2011;39(7):1914-1924.

 

Saul KR, Hayon S, Smith TL, Tuohy CJ, Mannava S. Postural dependence of passive tension in the supraspinatus following rotator cuff repair: a simulation analysis. Clin Biomech (Bristol, Avon). 2011;26(8):804-810.

 

Koman LA, Poehling GG, Smith BP, Smith TL, Chloros G. Complex regional pain syndrome In: Wolfe SW, Hotchkiss RN, Pederson WC, Kozin SH, eds. Green's operative hand surgery, vol 2. 6th ed. Philadelphia: Elsevier/Churchill Livingstone;2011: 1959-1988.

 

Koman LA, Smith BP, Smith TL, Ruch DS, Li Z. Vascular disorders In: Wolfe SW, Hotchkiss RN, Pederson WC, Kozin SH, eds. Green's operative hand surgery, vol 2. 6th ed. Philadelphia: Elsevier/Churchill Livingstone;2011: 2197-2240.

 

Patterson RW, Li Z, Smith BP, Smith TL, Koman LA. Complex regional pain syndrome of the upper extremity. J Hand Surg [Am]. 2011;36(9):1553-1562.

 

Stone AV, Ma J, Callahan MF, Smith BP, Garrett JP, Smith TL, Koman LA. Dose- and volume dependent-response to intramuscular injection of botulinum neurotoxin-A optimizes muscle force decrement in mice. J Orthop Res. 2011;29(11):1764-1770.

 

Mannava S, Plate JF, Whitlock PW, Callahan MF, Seyler TM, Koman LA, Smith TL, Tuohy CJ. Evaluation of in vivo rotator cuff muscle function after acute and chronic detachment of the supraspinatus tendon: an experimental study in an animal model. J Bone Joint Surg Am. 2011;93(18):1702-1711.

 

Mannava S, Plate JF, Stone AV, Smith TL, Smith BP, Koman LA, Tuohy CJ. Recent advances for the management of Raynaud phenomenon using botulinum neurotoxin A. J Hand Surg [Am]. 2011;36(10):1708-1710.

 

Carver KA, Smith TL, Gallagher PE, Tallant EA. Angiotensin-(1-7) attenuates angiotensin II-induced fibrosis through a reduction in connective tissue growth factor [abstract]. Hypertension. 2011;58(5):e178.

 

Nunez F, Trach S, Burnett L, Handa R, Van Dyke M, Callahan M, Smith T.Vasoactive properties of keratin-derived compounds. Microcirculation. 2011;18(8):663-669.

 

Smith TL, Callahan MF, Blum K, DiNubile NA, Chen TJH, Waite RL. H-Wave effects on blood flow and angiogenesis in longitudinal studies in rats. J Surg Orthop Adv. 2011;20(4):255-259.

 

Koman LA, Li Z, Smith BP, Smith TL. Complex regional pain syndrome: types I and II In: Skirven TM, Osterman AL, Fedorczyk J, Amadio PC, eds. Rehabilitation of the hand and upper extremity. 6th ed. Philadelphia: Elsevier Mosby;2011: 1470-1478.

 

Deal DN, Ma J, Apel P, Novak V, Carlson CS, Parker JB, Olson EJ, Rieser GR, Smith TL, Shilt JS. Effect of intra-articular pressurization associated with arthroscopy on the immature physis: investigation in an animal model. J Pediatr Orthop. 2010;30(1):21-25.

 

Li Z, Chloros GD, Smith BP, Smith TL, Koman LA. Management of upper extremity pain and vascular disorders In: Trumble TE, Rayan GM, Budoff JE, Baratz ME, eds. Principles of hand surgery and therapy. 2nd ed. Philadelphia: Saunders Elsevier;2010: 270-285.

 

Li Z, Smith BP, Tuohy C, Smith TL, Koman LA. Complex regional pain syndrome after hand surgery. Hand Clin. 2010;26(2):281-289.

 

Stabile KJ, Odom D, Smith TL, Northam C, Whitlock PW, Smith BP, Van Dyke ME, Ferguson CM. An acellular, allograft-derived meniscus scaffold in an ovine model. Arthroscopy. 2010;26(7):936-948.

 

Nunez F, Trach S, Kislukin V, Van Dyke M, Callahan M, Smith T, Koman LA.Comparison of hemodynamic changes after hemorrhage and treatment with hyperviscous fluids [abstract]. Shock. 2010;33(Suppl 1):16.

 

Carver KA, Smith TL, Gallagher PE, Tallant EA. Angiotensin-(1-7) reduces angiotensin II-induced remodeling of the microcirculation [abstract]. Hypertension. 2010;56(5):e141-e142.

 

Coldren FM, Palavecino EL, Levi-Polyachenko NH, Wagner WD, Smith TL, Smith BP, Webb LX, Carroll DL. Encapsulated Staphylococcus aureus strains vary in adhesiveness assessed by atomic force microscopy. J Biomed Mater Res A. 2009;89(2):402-410.

 

Smith TL, Blum K, Callahan MF, DiNubile NA, Chen TJH, Waite RL. H-Wave induces arteriolar vasodilation in rat striated muscle via nitric oxide-mediated mechanisms. J Orthop Res. 2009;27(9):1248-1251.

 

Apel PJ, Crane D, Northam CN, Callahan M, Smith TL, Teasdall RD. Effect of selective sensory denervation on fracture-healing: an experimental study of rats. J Bone Joint Surg Am. 2009;91(12):2886-2895.

 

Sierpinski P, Garrett J, Ma J, Apel P, Klorig D, Smith T, Koman LA, Atala A, Van Dyke M. The use of keratin biomaterials derived from human hair for the promotion of rapid regeneration of peripheral nerves. Biomaterials. 2008;29(1):118-128.

 

Li Z, Ma J, Apel P, Carlson CS, Smith TL, Koman LA. Brachial plexus birth palsy-associated shoulder deformity: a rat model study. J Hand Surg [Am]. 2008;33(3):308-312.

 

Chloros GD, Smerlis NN, Li Z, Smith TL, Smith BP, Koman LA. Noninvasive evaluation of upper-extremity vascular perfusion. J Hand Surg [Am]. 2008;33(4):591-600.

 

Brown JM, Bell TA III, Alger HM, Sawyer JK, Smith TL, Kelley K, Shah R, Wilson MD, Davis MA, Rudel LL, et al. Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss. J Biol Chem. 2008;283(16):10522-34.

 

Delo DM, Wang Z, Shaffer R, Guan X, Neshat S, Smith T, Callahan M, Groban L, Atala A, Soker S. Effects of human amniotic fluid derived stem cells on cardiac function after myocardial infarction [abstract]. Tissue Eng Part A. 2008;14(5):844.

 

Sierpinski P, Garrett J, Ma J, Apel P, Smith T, Atala A. Koman A [sic] [Koman L], Van Dyke M. Human hair derived keratins mediate Schwann cell behavior in vitro and facilitate rapid regeneration of peripheral nerves in vivo [abstract]. Tissue Eng Part A. 2008;14(5):859.

 

Whitlock PW, Smith TL, Shilt JS, Poehling GG, Van Dyke ME. A tissue-engineered tendon scaffold [abstract]. Tissue Eng Part A. 2008;14(5):698.

 

Apel PJ, Garrett JP, Sierpinski P, Ma J, Atala A, Smith TL, Koman LA, Van Dyke ME.Peripheral nerve regeneration using a keratin-based scaffold: long-term functional and histological outcomes in a mouse model. J Hand Surg [Am]. 2008;33(9):1541-1547.

 

Mulya A, Lee J-Y, Gebre AK, Boudyguina EY, Chung S-K, Smith TL, Colvin PL, Jiang X-C, Parks JS. Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL. J Lipid Res. 2008;49(11):2390-2401.

 

Seyler TM, Smith BP, Marker DR, Ma J, Shen J, Smith TL, Mont MA, Kolaski K, Koman LA. Botulinum neurotoxin as a therapeutic modality in orthopaedic surgery: more than twenty years of experience. J Bone Joint Surg Am. 2008;90(Suppl 4):133-145.

 

Whitlock P, Seyler T, Smith T, Poehling G, Koman LA. Effect of strain on a novel cell-seeded scaffold for tendon and ligament reconstruction [abstract]. In: Program Book of the 54th Annual Meeting of the Orthopaedic Research Society; 2008 Mar 2-5; San Francisco (CA). 2008;():1476.

 

Whitlock P, Poehling G, Smith T, VanDyke M, Shilt J. Development, characterization, and cell-seeding of a naturally-derived scaffold for tendon and ligament resconstruction [abstract]. In: Program Book of the 54th Annual Meeting of the Orthopaedic Research Society; 2008 Mar 2-5; San Francisco (CA). 2008;():1481.

 

Callahan MF, Kislukhin VK, Thuramalla NV, Krivitski NM, Smith TL. Novel technique for estimation of hemodynamic status of rats during hemorrhage and resuscitation [abstract]. FASEB J. 2007;21(6):A1259.

 

Langfitt M, Webb L, Smith TL. Microvascular effects of therapeutic topical negative pressure application (TNPA) [abstract]. FASEB J. 2007;21(5):A486.

 

Norris JA, Cabrera MN, Smith TL, Reeves SH, Koman LA. Quantifying spasticity in a clinical setting. Biomed Sci Instrum. 2007;43():284-289.

 

Sierpinski P, Garrett J, Ma J, Apel P, Smith T, Atala A, Koman LA, Van Dyke M.Human hair derived keratins mediate Schwann cell behavior in vitro and facilitate rapid peripheral nerve regeneration in vivo [abstract]. FASEB J. 2007;21(6):A1273.

 

Whitlock PW, Smith TL, Shilt JS, Poehling GG, Van Dyke ME. Development, characterization and cell-seeding of a novel biocompatible scaffold for tendon and ligament reconstruction [abstract]. FASEB J. 2007;21(5):A268.

 

Gmeiner WH, Garg S, Hatcher HC, Smith TL, Bourland JD, Garg PK. MicroPET imaging to monitor tumor response to single agent and combined ionizing radiation therapy and FdUMP treatment [abstract]. J Nucl Med. 2007;48(6 Suppl 2):83P.

 

Lee J-Y, Badeau RM, Mulya A, Boudyguina E, Gebre AK, Smith TL, Parks JS.Functional LCAT deficiency in human apolipoprotein A-I transgenic, SR-BI knockout mice. J Lipid Res. 2007;48(5):1052-1061.

 

Whitlock PW, Smith TL, Poehling GG, Shilt JS, Van Dyke M. A naturally derived, cytocompatible, and architecturally optimized scaffold for tendon and ligament regeneration. Biomaterials. 2007;28(29):4321-4329.

 

Sierpinski P, Garrett J, Ma J, Apel P, Smith T, Atala A, Koman LA, Van Dyke M.Human hair derived keratins facilitate regeneration of peripheral nerves in vivo [abstract]. Tissue Eng. 2007;13(7):1706-1707.

 

Ma J, Shen J, Smith BP, Ritting A, Smith TL, Koman LA. Bioprotection of tendon repair: adjunctive use of botulinum toxin A in Achilles tendon repair in the rat. J Bone Joint Surg Am. 2007;89(10):2241-2249.

 

Ma J, Shen J, Garrett JP, Lee CA, Li Z, Elsaidi GA, Tan KH, Smith TL, Smith BP, Koman LA, et al. Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model. J Orthop Res. 2007;25(11):1498-1505.

 

Stone AV, Ma J, Whitlock PW, Koman LA, Smith TL, Smith BP, Callahan MF.Effects of Botox and Neuronox on muscle force generation in mice. J Orthop Res. 2007;25(12):1658-1664.

 

Ward WG, Smith TL, Rosencrance E, Deal DN, Dickerson E, Holsenbeck S. Soft tissue ingrowth in metal rods with varying surface textures and its clinical significance. Mater Sci Forum. 2007;539-543():545-546.

 

Stabile KJ, Whitlock PW, Smith TL, VanDyke ME, Ferguson CM. A tissue engineered meniscus scaffold [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007;():222.

 

Whitlock PW, Knutson J, Smith TL, Van Dyke ME, Shilt JS, Koman LA, Poehling GG.Effects of mechanical stimulation on a cell-seeded scaffold developed for tendon and ligament regeneration [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007;():391.

 

Apel PJ, Garrett J, Sierpinski P, Ma J, Hick J, Smith TL, Koman LA, Van Dyke ME.Peripheral nerve regeneration using a keratin gel-based scaffold: long-term functional and histological outcomes in a mouse model [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007;():364.

 

Whitlock PW, Smith TL, Shilt JS, Van Dyke ME, Poehling GG. A novel scaffold for tendon and ligament regeneration derived from human allograft tissue [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007;():188.

 

Sierpinski PL, Garrett J, Ma J, Apel PJ, Smith T, Koman LA, Atala A, Van Dyke M. A biomaterial derived from human hair keratins can serve as a scaffold for tissue engineering in orthopaedic applications [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007;():61.

 

Sierpinski PL, Apel PJ, Burnell JM, Klorig D, Smith T, Koman LA, Atala A, Van Dyke M. Keratin biomaterials made from human hair mediate Schwann and endothelial cell activity in vitro [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007;():417.

 

Whitlock PW, Smith TL, Shilt JS, Poehling GG, Van Dyke ME. Development of a biocompatible scaffold for tendon and ligament regeneration [abstract]. In: Transactions Online of the 53rd Annual Meeting of the Orthopaedic Research Societies; 2007 Feb 11-14; San Diego (CA). 2007;32():0333.

 

SYNOPSIS OF AREA OF INTEREST: The overall areas of interest in this laboratory are microcirculation of thermoregulation and inflammation, hemodynamics, peripheral nerve injury and repair, skeletal muscle adaptation to injury, diabetes, microsurgery, wound care, and tissue reconstruction. DETAILED AREA OF INTEREST: Research in the Department of Orthopaedic Surgery covers many disciplines. Current projects in collaboration with the Wake Forest Institute for Regenerative Medicine include the following: The use of tissue engineered constructs for repair of significant peripheral nerve gaps following injury. Small silastic conduits are filled with keratose gels and used to repair tibial nerve gaps in mice. These preliminary constructs result in improved nerve conduction velocity distal to the injury, increase amplitude of EMG, and improved muscle force generation with nerve stimulation. Murine models of nerve injury provide reproducible test beds for these engineered constructs. Tissue engineered allografts for ACL, tendon, and meniscus repairs. Techniques for decellularizing and repopulating these allograft tissues are being developed to reduce immunogenicity and improve graft incorporation and remodeling by the recipient. Engineered structures then can be implanted in appropriate animal models (sheep, rabbit, mice) to evaluate in vivo incorporation. Murine models of myocardial infarction to test stem cell therapies utilizing coronary artery ligations performed as survival surgeries in mice. These ligations produce predictable lesions of the myocardium which can subsequently be injected with myocardial progenitor cells in an effort to reduce the degree of myocardial deficits accompanying infarction. Assessment of cardiac function in the mice to determine myocardial recovery with and without therapy is performed using ventricular pressure-volume loops and ultrasound imaging.

 

Coming soon . .