Robert Sigler, DVM, PhD, DACVP

Robert Sigler

Role

IVAC Pathology
ULAM Faculty

Job Title

Director, In-Vivo Animal Core

Additional Titles

Clinical Professor, Unit for Laboratory Animal Medicine (ULAM)

Profile

Dr. Sigler has worked in the pharmaceutical industry since 1987 as a toxicologist pathologist at Parke-Davis, Esperion, and Pfizer. He has experience on multiple discovery and development teams and as a study director and study pathologist working with anti-infectives, small molecules and macromolecules for atherosclerosis, and small molecule and nanoparticle cancer chemotherapies. He managed the Esperion vivarium, designing efficacy and safety studies. Dr. Sigler founded a CRO in 2009 which designed and performed pre-clinical efficacy and safety studies for several indications including atherosclerosis, diabetes, obesity, autoimmune diseases and cancer.

Recently, he has served as a consultant regarding lupus nephritis models for Janssen labs and evaluating bone stabilization devices and IBD models for multiple companies. Dr. Sigler has also been a contract pathologist for Van Andel Research Institute, the device-testing CRO, Wuxiapptec, and Charles River Labs. In his role as Director of the In-Vivo Animal Core (IVAC), Dr. Sigler oversees the only core on U-M's campus dedicated exclusively to the research histology of animal models through intepretive services offered by board-certified veterinary pathologists.

Professional Background

  • BS, University of Michigan (Physical Anthropology and Zoology Major)
  • DVM (Doctor of Veterinary Medicine) Michigan State University
  • PhD (Pathology), University of Maryland Medical School
  • Veterinary Pathology Residency at University of Tennessee College of Vet Med
  • Diplomate, American College of Veterinary Pathologists
     
  1. Henninger, R. and Sigler, RE.: Spinal dysraphism in a holstein calf. Compendium of Veterinary Continuing Education, 5:488 492, 1983.
     
  2. Linnabary, R., Fetcher, A. and Sigler, R.: Acute pulmonary emphysema in a cow. Mod. Vet. Pract.,65: 849 851, 1984.
     
  3. Craig, J.M., Sigler, R.E. and Walker, M.: The effects of intraoperative radiation on healing of gastric and urinary incisions in the dog. Am. J. Vet. Res., 46: 1647 1652, 1985.
     
  4. Potgieter, L.N.D., Sigler, R.E. and Russell, R.G.: Pneumonia in Ottoman vipers (Vipera xanthena xanthena) associated with a parainfluenza 2 like virus. J. Wildlife Dis. 23:355 360, 1987.
     
  5. Sigler, R.E., Jones, R.T., Hebel, J.R. and McDowell, E.M.: Hamster tracheal organ culture in serum-free media: A quantitative comparison of in vitro epithelial morphology with that of in vivo controls. In Vitro:  Cell. Dev. Biol., 23:100 110, 1986.
     
  6. Sigler, R.E., Banks Schlegel, S.P., and McDowell E.M.: Epithelial migration in human bronchial and hamster tracheal organ explant cultures. Epithelia, 1:267 283, 1987.
     
  7. Sigler, R.E., Newkirk, C., and McDowell, E.M.: Histogenesis and morphogenesis of epidermoid metaplasia in hamster tracheal organ explant culture. Virchows Archiv. Cell Pathol., 55:47 55, 1988.
     
  8. Field, K.J., Griffin H.E., Sigler, R.E.: Abdominal parasites in an Asian Macaque. Lab Animal Sci., 41:504-505, 1991.
     
  9. Saby, J.A., Sigler, R.E., and Stever, K. Comparison of fixatives for histologic evaluation of the canine eye. J. Histotechnol., 14:251-255, 1991.
     
  10. Dominick, M.A., Robertson, D.G., Bleavins, M.R., Sigler, R.E., Bobrowski, W.F. and Gough, A.W. a 2µ globulin Nephropathy without nephrocarcinogenesis in male Wistar rats administered gabapentin. Tox. Appl. Pharm., 111:375-387, 1991.
     
  11. Sigler, R.E., Dominick, MA. and McGuire, E.J. Subacute toxicity of a halogenated pyrrole Hydroxymethylglutaryl-CoA reductase inhibitor in Wistar rats. Toxicol. Pathol., 20:595-602, 1992.
     
  12. Gough, A.W., Kasali, O.B., Sigler, R.E., and Baragi, V.J. Quinolone Arthropathy-Acute Toxicity to Immature Articular Cartilage. Toxicol. Pathol., 20:436-449, 1992.
     
  13. Robertson, D., Loewen, G., Walsh, K.M., Dethloff, L.A., Sigler, R.E., Dominick, M.A., Urda, E.R. Subacute and subchronic toxicology studies of CI-986, a novel anti-inflammatory compound. Fund. Appl. Tox., 20:446-455, 1993.
     
  14. Sigler, R.E., Gough, A.W., and de la Iglesia, F.A. Pancreatic acinar cell neoplasia in male Wistar rats following 2 years of gabapentin exposure. Toxicology 98:73-82, 1995.
     
  15. Hansen, J.F., Ross, P.E., Makovec, G.T., Eustis, S.L., and Sigler, R.E. Proliferative and other selected lesions of the Exocrine Pancreas in Rats. In Guides for Toxicologic Pathology. STP/ARP/AFIP, Washington, DC, 1995.
     
  16. Fowler, M.L., Sigler, R.E., de la Iglesia, F.A., Reddy, J.K., and Lalwani, N.D. Absence of Ki-ras mutations in exocrine pancreatic tumors from male rats chronically exposed to gabapentin. Mut. Res. 327:151-160, 1995.
     
  17. Gough, A., Johnson, R., Campbell, E., Hall, L., Tyler, J., Carpenter, A., Black, W., Basrur, P.K., Baragi, V.M., Sigler, R. and Metz, A. Quinolone arthropathy in immature rabbits treated with the fluoroquinolone, PD 117596. Exp. Toxic. Pathol. 48:225-232, 1996.
     
  18. Gough, A., Johnson, R.J., Campbell, E., Hall, L.J., Tylor, J., Carpenter, A., Black, W.D., Basrur, P.K., Baragi, V., Sigler, R.E., and Metz, A.L. Quinolone arthropathy in immature rabbits treated with the fluoroquinolone PD 117596. Exptl Toxicol. Pathol 48, 225-232, 1996.
     
  19. Baragi VM, Renkiewicz RR, Qiu L, Brammer D, Riley JM, Sigler RE, Frenkel SR, Amin A, Abramson SB, Roessler BJ: Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo. Osteoarthritis Cart. 5 (4): 275-282, 1997. 
     
  20. Dethloff, L.A., Barr, B.M., Bestervelt, L.L, Sigler, R.E., LaGattuta, M.S. de la Iglesia, F.A. Gabapentin-induced mitogenic activity in rat pancreatic acinar cells. Toxicological Sciences, 55, 52-59, 2000.
     
  21. Johnson, R.J., Black, W.D., Sigler, R.E., Baragi, V.M., and Gough, A.W. Evaluation of toxicokinetic variables and arthropathic changes in juvenile rabbits after oral administration of an investigational fluoroquinolone, PD 117596. Amer Jour Vet Research 61:1396-1402, 2000.
     
  22. Robertson, D.G., Reily, M.D., Sigler, R.E., Wells, D., Patterson, D., and Braden, T.K. Metabonomics: Evaluation of nuclear magnetic resonance (NMR) and pattern recognition technology for rapid in vivo screening of liver and kidney toxicants. Toxicological Sciences 57: 326-337, 2000.
     
  23. Cadillac, J.M., Sigler, R.E., Weinberg, J.B., Lutzke, M.L., and Rockford, R. Gammaherpesvirus-induced lung pathology is altered in the absence of macrophages. Lung. 183(4):239-251, 2005.
     
  24. Vergara, M, Smith-Wheelock, M., Harper, J.M., Sigler, R., and Miller, R.A. Hormone-treated snell dwarf mice regain fertility but remain long lived and disease resistant. Journal of Gerontology 59A: 1244-1250, 2004.
     
  25. Miller, R.A., Buehner, G., Chang, Y., Harper, J.M., Sigler, R., and Smith-Wheelock, M. Methionine-deficient diet extends mouse life span, slow immune and lens aging, alters glucose, T4, IGF-1 and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4: 119-125, 2005.
     
  26. Zhang, Y-W., Su, Y., Lanning, N., Swiatek, P., Bronson, R.T., Sigler, R., Martin, P., and Vande Woude, G.F. Targeted disruption of Mig-6 in the mouse genome leads to early onset degenerative joint disease. PNAS 102: 11741-11745, 2005.
     
  27. Holmen SL, Zylstra CR, Mukerjee A, Sigler RE, Faugere MC, Bouxsein ML, Deng L, Clemens TL, Williams BO. Essential role of beta-catenin in postnatal bone acquisition. J. Biol. Chem. 280 (22):21162-21168, 2005.
     
  28. Lester P.A., Rush, H.G., Sigler R.E. Renal transitional cell carcinoma and choristoma in a degu (Octodon degus). Contemp. Top Lab Anim. Sci. 44(3):41-44, 2005.
     
  29. Moshitch-Moshkovitz, S., Tsarfaty, G., Kaufman, D., Stein, G.Y., Shichrur, K., Sigler, R.E., Resau, J.H, Vande Woude, G.F., and Tsarfaty, I. In Vivo Molecular imaging of early tumorigenesis and malignant progression induced by transgenic expression of GFP-Met. Neoplasia 8: 353-363, 2006.
     
  30. McDuffie, E.M., Obert, L., Chupka, J., and Sigler, R. Detection of cytokine protein expression in mouse lung homogenates using suspension bead array. J Inflamm. 3: 15-25, 2006.
     
  31. Zhang, Y-W., Stall, B. Su, Y., Swiatek, P., Zhao, P., Cao, B., Resau, J., Sigler, R., Bronson, R., and Vande Woude, G.F. Evidence that MIG-6 is a tumor suppressor gene. Oncogene 26: 269-276, 2007.
     
  32. Baxi, S., Crandall, D.L., Meier, T.R., Wrobleski, S., Hawley, A., Farris, D., Elokdah, H., Sigler, R., Schaub, R.G., Wakefield, T., and Myers, D. Dose-dependent thrombus resolution due to oral PAI-1 inhibition with tiplaxtinin in a rat stenosis model of venous thrombosis. Throm Haemost. 2008 Apr; 99(4):749-758, PMID: 18392333.
     
  33. Xie, Q., Thompson, R., Hardy, K., DeCamp, L., Berghuis, B., Sigler, R., Knudsen, B., Cottingham, S., Zhao, P., Cykema, K., Cao, B., Resau, J., Hay, R., and Vande Woude, G.F. A highly invasive human glioblastoma pre-clinical model for testing therapeutics. J. of Translational Med 6: 77-89, 2008.
     
  34. Moore, R, Hawley, A, Sigler, R, Farris D, Wrobleski S, Ramacciotti E, Myers D. Tissue inhibitor of metalloproteinase-1 is an early marker of acute endothelial dysfunction in a rodent model of venous oxidative injury. Ann Vasc Surg. 2009 Jul-Aug; 23(4):498-505. Epub 2009 May 21; PMID: 19467832
     
  35. Graveel, C.R., DeGroot, J.D., Sigler, R.E., and Vande Woude, G.F. Germline Met mutations in mice reveal mutation- and background-associated differences in tumor profiles. PloS ONE 5(10):e13586
     
  36. Alvarado, C.M., Diaz, J.A., Hawley, A.E., Wroblestki, S.K., Sigler, R.E., Myers, D.D.Jr. Male mice have increased thrombotic potential: Sex differences in a mouse model of venous thrombosis. Thromb Res 2011 May: 127(5): 468-86; PMID: 21296387.
     
  37. Hampton, AL, Diaz, JA, Hawley, AE, Wrobleski, SK, Sigler, RE, Myers, DD Jr. Myeloid cell tissue factor does not contribute to venous thrombogenesis in an electrolytic injury model. Thromb Res 2011 Dec 20; PMID: 22192154.
     
  38. Culmer, DL, Diaz, JA, Hawley, AE, Jackson, TO, Shuster, KA, Sigler, RE, Wakefield TW, Myers DD Jr. Circulating and vein wall P-selectin promote venous thrombogenesis during aging in a rodent model. Thromb Res. 2013 Jan; 131(1):42-8. PMID: 231746424 [PubMed}.
     
  39. Shuster, KA Wrobleski SK, Hawley AE, Luccesi, BR, Sorenson DR, Bergin IL, Sigler, RE, Guire, KE, Nowland, MH, Wakefield, TW, Myers DD Jr. Prothrombotic effects of thrombolytic therapy in a rat (Rattus norvegicus) model of venous thrombolysis. Comparative Medicine, 2013, 63: 244-251
     
  40. Monks, NR, Cherba, DM, Kamerline SG, Simpson, H, Rusk, AW, Carter D, Eugster, E, Mooney, M, Sigler, R, Steensma, M, Grabinski, T, Marotti, KR, Webb, CP. A multi-site feasibility study for personalized medicine in canines with psteosarcoma (OSA), Journal of Translational Medicine, 2013, 11: 158
     
  41. Kernodle, S., Converso-Baran, K., Nemzek, J., Wilkinson, J.E., Sigler, R.E., and Markham, B.E. Chronic dosing with membrane sealant Polaxemer 188 improves cardiac and respiratory dysfunction in the mdx mouse model of Duchenne muscular dystrophy. Neuromuscular Disorder, submitted for publication.