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Faculty Detail    
Name KEVIN AARON ROTH
 
Campus Address WP P210 Zip 7331
Phone 205-934-5802
E-mail karoth@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Pathology Gen Administration Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Secondary  Neurobiology  Neurobiology Professor
Center  Center for Aging  COMPREHENSIVE CTR FOR HEALTHY AGING Professor
Center  Civitan International Research Center  Civitan International Research Center Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Professor
Center  Ctr for Glial Bio in Med  Ctr for Glial Bio in Med Professor
Center  Neurology   Ctr Neurodegeneration & Exp Ther (CNET) Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Integrative Biomedical Sciences 
Integrative Genetics Graduate Program 
Medical Scientist Training Program 
Molecular and Cellular Pathology Program 
Neuroscience 
Neuroscience Graduate Program 
Neurosciences 

Biographical Sketch 
Dr. Roth graduated with highest honor from the University of Michigan and received his M.D. and Ph.D. in neuroscience from Stanford University School of Medicine. He completed his pathology residency and neuropathology fellowship at Washington University in St. Louis before joining the Washington University faculty in 1989. He was selected Lecturer of the Year three times, received seven Distinguished Teaching Service Awards, and was promoted to the rank of full professor in the Departments of Pathology and Immunology, and Molecular Biology and Pharmacology at Washington University in 2001. Dr. Roth moved to UAB in 2002 and served as Director of the Division of Neuropathology until his appointment as Chair of Pathology in 2008. He was the founding Director of the UAB Comprehensive Neuroscience Center and he currently serves as Director of the Alabama Neuroscience Blueprint Center and as the Robert and Ruth Anderson Professor and Chair of the Department of Pathology.

Society Memberships
Organization Name Position Held Org Link
American Association of Neuropathologists    www.neuropath.org 
American Society for Investigative Pathology  Councilor; Associate Editor, American Journal of Pathology  www.asip.net 
Histochemical Society  Associate Editor, Journal of Histochemistry and Cytochemistry  www.histochemicalsociety.org 
Society for Neuroscience    www.sfn.org 

Research/Clinical Interest
Title
Molecular Regulation of Neuronal Cell Death
Description
Research in my laboratory is focused on the regulation of neuronal apoptosis. Neuronal apoptosis occurs during normal nervous system development and in a variety of neuropathological processes including hypoxic/ischemic injury and neurodegenerative diseases. We have used mice with targeted gene disruptions of specific bcl-2 and caspase family members, in combination with a variety of in vivo and in vitro models of neuronal cell death, to define the cell- and stimulus-specific molecular pathways of cell death. We have demonstrated that normal nervous system development is regulated by APAF-1-, caspase-9-, and caspase-3-dependent apoptosis of neural precursor cells and Bax:Bcl-XL-dependent apoptosis of immature neurons. Neural precursor cell apoptosis also plays an important role in preventing neural tumorigenesis and is triggered by DNA damage. The long-term goals of my laboratory are to define the molecular pathways of apoptotic and autophagic neuronal death during brain development and in neuropathological conditions and to subsequently design pharmacological strategies for affecting the death process. Such studies will yield significant new data on the cellular and molecular regulation of neuronal cell death and hopefully, provide insights into the prevention and treatment of strokes, neurodegenerative diseases and brain tumors.

Selected Publications 
Publication PUBMEDID
Srinivasan A, Roth KA, Sayers RO, Shindler KS, Wong AM, Fritz, L.C., Tomaselli KJ: In situ immunodetection of activated caspase-3 in apoptotic neurons in the developing nervous system. Cell Death and Differentiation. 1998; 5:1004-1016.  9894607 
Goping IS, Gross A, Lavoie JN, Nguyen M, Jemmerson R, Roth K, Korsmeyer SJ, Shore GC: Regulated targeting of BAX to mitochondria. J. Cell Biol., 1998; 143(1):207-215.   9763432 
Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P: Apaf-1 (CED-4 homologue) regulates programmed cell death in mammalian development. Cell, 1998; 94:727-737. PMID: 9753320  9753320 
Schmidt RE, Dorsey DA, Selznick LA, DiStefano PS, Carroll SL, Beaudet LN, Roth KA: Neurotrophin sensitivity of prevertebral and paravertebral rat sympathetic autonomic ganglia. J. Neuropath. Exp. Neurol., 1998; 57:158-167.  9600208 
Weck KE, Dal Canto AJ, Gould JD, O'Guin AK, Roth KA, Saffitz JE, Speck SH, Virgin HW: Murine gamma-herpesvirus 68 causes severe large vessel arteritis in mice lacking interferon-gamma responsiveness: A new model for virus induced vascular disease. Nature Medicine, 1997; 3:1346-1353.   9396604 
Roth KA, Brenner JW, Selznick LA, Gokden M, Lorenz RG: Enzyme-based antigen localization and quantitation in cell and tissue samples (Midwestern Assay). J. Histochem. Cytochem., 1997; 45:1629-1641.   9389766 
Gökden M, Roth KA, Carroll SL, Wick MR, Schmidt RE: Clear cell neoplasms and pseudoneoplastic lesions of the central nervous system. Seminars in Diagnostic Path. 1997; 14(4):253-269.   9383825 
Schmidt RE, Dorsey D, Parvin CA, Beaudet LN, Plurad SB, Roth KA: Dystrophic axonal swellings develop as a function of age and diabetes in human dorsal root ganglia. J. Neuropathol. Exp. Neurol. 1997; 56:1028-1043.   9291944 
Shirasawa S, Yunker AMR, Roth KA, Brown GA, Horning S, Korsmeyer SJ: Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon. Nature Medicine 1997; 3:646-650.   9176490 
Shindler KS, Latham CB, Roth KA: bax deficiency prevents the increased cell death of immature neurons in bcl-x-deficient mice. J. Neurosci. 1997; 17:3112-3119.   9096145 
Ardelt AA, Karpitskiy VV, Krause JE, Roth KA: The neostriatal mosaic: Basis for the changing distribution of neurokinin-1 receptor immunoreactivity during development. J. Comp. Neurol. 1996; 376:463-475. PMID: 8956111  8956111 
Shindler KS, Roth KA: Double immunofluorescent staining using two unconjugated primary antisera raised in the same species. J. Histochem. Cytochem. 1996; 44:1331-1335. PMID: 8918908  8918908 
Linette GP, Li Y, Roth K, Korsmeyer SJ: Cross talk between cell death and cell cycle progression: Bcl-2 regulates NFAT-mediated activation. Proc. Natl. Acad. Sci. (USA) 1996; 93:9545-9552.   8790367 
Torack RM, Roth KA, Miller JW: Neuronal argyrophilia and phosphorylated neurofilament accumulation secondary to deafferentation. J. Neuropath. Exp. Neurol. 1996; 55:466-470. PMID: 8786406  8786406 
Roth KA, Motoyama N, Loh DY: Apoptosis of bcl-x deficient telencephalic cells in vitro. J. Neurosci. 1996; 16:1753-1758. PMID: 8774443  8774443 
Shindler KS, Roth KA: Cholera toxin binds to differentiating neurons in the developing murine basal ganglia. Dev. Brain Res. 1996; 92:199-211. PMID: 8738127  8738127 
Tornusciolo DRZ, Schmidt RE, Roth KA: Simultaneous detection of TDT-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells and multiple immunohistochemical markers in single tissue sections. BioTechniques, 1995; 19:800-805. PMID: 8588920  8588920 
Kovalic JJ, Flaris N, Grigsby PW, Pirkowski M, Simpson JR, Roth KA: Intracranial ependymoma; long term outcome, patterns of failure. J Neuro-Oncology 1993; 15:125-131. PMID: 8509817  8509817 
Falk P, Roth KA, Boren T, Westblom TU, Gordon JI, Normark S: An in vitro adherence assay reveals that Helicobacter pylori exhibits cell lineage specific tropism in the human gastric epithelium. Proc. Natl. Acad. Sci. (USA) 1993; 90:2035-2039. PMID: 8383333  8383333 
Simon TC, Roth KA, Gordon JI: Use of transgenic mice to map cis-acting elements in the liver fatty acid binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. J. Biol. Chem. 1993; 268:18345-18358. PMID: 8349710  8349710 
Schmidt RE, Plurad SB, Parvin CA, Roth KA: The effect of diabetes and aging on human sympathetic autonomic ganglia. Am. J. Pathology 1993; 143:143-153. PMID: 8317545  8317545 
Kim SH, Roth KA, Moser AR, Gordon JI: Transgenic mouse models that explore the multistep hypothesis of intestinal neoplasia. J. Cell Biol. 1993; 123:877-893. PMID: 8227147  8227147 
Aiken KD, Yu W, Wright JR, Roth KA: Adaptation of enteroendocrine cells in response to jejunal-ileal transposition in the rat. Gastroenterology 1994; 106:1576-1583. PMID: 8194704  8194704 
Kim SH, Roth KA, Coopersmith CM, Pipas JM, Gordon JI: Expression of wild-type and mutant Simian virus 40 T antigens in villus-associated enterocytes of transgenic mice. Proc. Natl. Acad. Sci. (USA) 1994; 91:6914-6918. PMID: 8041720  8041720 
Falk P, Roth KA, Gordon JI: Lectins are sensitive tools for defining the differentiation programs of mouse gut epithelial cell lineages. Am. J. Physiol. 1994;266:G987-1003. PMID: 8023947  8023947 
Boren T, Falk P, Roth KA, Larson G, Normark S: Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 1993; 262:1892-1895. PMID: 8018146  8018146 
Ohara S, Roth KA, Beaudet LN, Schmidt RE: Transganglionic neuropeptide-Y response to sciatic-nerve injury in young and aged rats. J. Neuropathol. Exp. Neurol. 1994; 53:646-662. PMID: 7964905  7964905 
Ardelt AA, Flaris NA, Roth KA: Neurotrophin-4 selectively promotes survival of striatal neurons in organotypic slice culture. Brain Res. 1994; 647:340-344. PMID: 7922509  7922509 
Motoyama N, Wang F, Roth KA, Sawa H, Nakayama KI, Nakayama K, Negishi I, Senju S, Zhang Q, Fujii S, Loh DY: Massive cell death of immature hematopoietic cells and neurons in Bcl-x deficient mice. Science 1995; 267:1506-1510. PMID: 7878471  7878471 
Aiken KD, Kisslinger JA, Roth KA: Immunohistochemical studies indicate multiple enteroendocrine cell differentiation pathways in the mouse proximal small intestine. Developmental Dynamics 1994; 202:63-70. PMID: 7803848  7803848 
Molleston MC, Moran CJ, Roth KA, Rich KM: Infantile Meningioma. Pediatr. Neurosurg. 1994;21:195-200. PMID: 7803311  7803311 
Flaris NA, Shindler KS, Kotzbauer PT, Chand P, Ludwig CP, Konstantinidou AD, Roth KA: Developmentally-regulated lectin binding in the embryonic mouse telencephalon. Brain Research 1995; 678:99-109. PMID: 7620904  7620904 
Katz RJ, Roth KA, Schmaltz K: Tail pinch facilitation of self-stimulation in the rat--dependence upon dopamine and independence of opiates. Pharmacol. Biochem. Behav. 1980; 12:389-391. PMID: 7393937  7393937 
Katz RJ, Roth KA, Schmaltz K, Sible M: Interaction of stress and morphine in the rat using a classical conditioning design. Behav. Neural. Biol. 1980; 28:366-371. PMID: 7362593  7362593 
Katz RJ, Turner BB, Roth KA, Caroll BJ: Adrenergic control of motor activity: effects of PNMT inhibition upon open field behavior in the rat. Pharmacol. Biochem. Behav. 1978; 9:417-420. PMID: 733828  733828 
Mefford IN, Roth KA, Paxinos G, Barchas JD: Central and peripheral contributions to hypothalamic epinephrine. Brain Research 1981; 224:175-179. PMID: 7284834  7284834 
Roth KA, Katz RJ, Sibel M. Mefford IN, Barchas JD, Carroll BJ: Central epinergic inhibition of corticosterone release in rat. Life Sci. 1981;28:2389-2394. PMID: 7253827  7253827 
Mefford IN, Roth KA, Barchas JD: In Vivo MAO inhibition by SKF-64139--a potent PNMT inhibitor. Eur. J. Pharmacol. 1981; 70:345-353. PMID: 7227455  7227455 
Roth KA, Katz RJ, Schmaltz K, Sibel M: Reduced behavioral activity due to opiate blockade: relations to stress. Internatl. J. Neurosci. 1981; 12:59-62. PMID: 7203820  7203820 
Katz RJ, Roth KA, Schmaltz K: Amphetamine and tranylcypromine in an animal model of depression--pharmacological specificity of the reversal effect. Neurosci. Biobehav. Rev. 1981; 5:259-264. PMID: 7196556  7196556 
Roth KA, Katz RJ: Further studies on a novel animal model of depression--therapeutic effects of a tricyclic antidepressant. Neurosci. Biobehav. Rev. 1981; 5:253-258. PMID: 7196555  7196555 
Katz RJ, Roth KA, Carroll BJ: Acute and chronic stress effects on open field activity in the rat: Implications for a model of depression. Neurosci. Biobehav. Rev. 1981; 5:247-251. PMID: 7196554  7196554 
Roth KA, McIntire SL, Barchas JD: Nicotinic-catecholaminergic interactions in rat brain - Evidence for cholinergic, nicotinic and muscarinic interactions with hypothalamic epinephrine. J. Pharm. Exp. Ther. 1982; 221:416-420. PMID: 7077536  7077536 
Roth KA, McIntire SL, Lorenz RG, Barchas JD: Hypothalamic catecholamine changes under acute stress occur independently of nicotinic stimulation. Neurosci. Letters 1982; 28:47-50. PMID: 7063143  7063143 
Mefford IN, Roth KA, Barchas JD: Changes in rat hypothalamic and brainstem catecholamine concentrations following acute administration of PNMT inhibitors. Neurosci. Lett. 1980; 20:67-71. PMID: 7052550  7052550 
Roth KA, Weber E and Barchas JD: Immunoreactive corticotropin releasing factor (CRF) and vasopressin are colocalized in a subpopulation of the immunoreactive vasopressin cells in the paraventricular nucleus of the hypothalamus. Life Sciences 1982; 31:1857-1860. PMID: 6984129  6984129 
Roth KA, Evans CJ, Lorenz RG, Weber E, Barchas JD, Chang J-K: Identification of gastrin releasing peptide related substances in guinea pig and rat brain. Biochem. Biophys. Res. Comun. 1983; 112:528-536. PMID: 6847667  6847667 
Roth KA, Weber E, Barchas JD: Distribution of gastrin-releasing peptide/bombesin-like immunostaining in rat brain. Brain Research 1982; 251:277-282. PMID: 6754003  6754003 
Roth KA, Evans CJ, Weber E, Barchas JD, Bostwick DG, Bensch KG: Gastrin releasing peptide-related peptides in a human malignant lung carcinoid. Cancer Research 1983; 43:5411-5415. PMID: 6616473  6616473 
Bostwick DG, Roth KA, Barchas JD, Bensch KG: Gastrin releasing peptide immunoreactivity in intestinal carcinoids. Am. J. Clin. Pathol. 1984; 82:428-431. PMID: 6475838  6475838 

Keywords
Apoptosis, Autophagy, Bcl-2, Caspases, Neurodegenerative Disease, Neuropathology, Programmed cell death