Kevin A. Roth, MD, PhD

Departments And Divisions

  • Department of Pathology & Cell Biology
  • Donald W. King, MD and Mary Elizabeth King Professor of Pathology and Cell Biology
  • Chair, Department of Pathology and Cell Biology
  • Pathologist-in-Chief, NewYork-Presbyterian Hospital
Kevin A. Roth, <span>MD, PhD</span>

Research in my laboratory is focused on defining the molecular pathways regulating neuronal cell death during development and in neuropathological conditions. Using a combination of unique transgenic mouse models, sensitive detection methods, in vitro model systems and human samples, our laboratory helped define the role of both apoptotic and non-apoptotic cell death pathways in development and neurodegenerative disease. Most recently, we have focused on the cellular origins of malignant glial tumors of the central and peripheral nervous systems and the mechanisms of chemotherapy-induced tumor cell death.

Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in patients with neurofibromatosis type 1 (NF1) and are notoriously difficult to treat. Radiotherapy and chemotherapy have proven largely ineffective and median MPNST patient survival is approximately five years. We have been investigating the utility of a variety of agents including tamoxifen, BH3 mimetics, and lysosomtropic agents to induce cell death in human MPNST cell lines in vitro and in transgenic mouse models of MPNSTs in vivo. We are attempting to define the cellular and molecular pathways regulating MPNST responsiveness to chemotherapeutic agents and to develop novel MPNST prevention and treatment strategies.

Another project in the laboratory is to elucidate the role of autophagy in promoting glioblastoma (GBM) survival and/or cell death. Our ongoing studies have revealed that autophagy induction can be either survival promoting or death inducing depending on tumor and treatment specific factors. We are actively investigating combinatorial therapies to manipulate the autophagy-lysosomal pathway to enhance tumor cell cytotoxicity in specific subsets of GBMs. In total, these investigations will further refine our understanding of cell death regulation and potentially lead to more effective therapies for malignant glial neoplasms.

    Education & Training

  • MD, Stanford University School of Medicine
  • Residency: Barnes Jewish Hospital

Lab Locations

  • Presbyterian Hospital Building (PH)

    622 West 168th Street
    Suite 1564
    New York, NY 10032
    Phone:
    (212) 305-9134
    Fax:
    (212) 342-3013
    Email:
    karoth@columbia.edu

Contact Info

Past Positions

9/2015 – Present    Chair and Donald W. King, M.D. and Mary Elizabeth King, M.D. Professor of Pathology and Cell Biology, Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY

9/2015 – Present    Pathologist in Chief, NewYork-Presbyterian/Columbia University Medical Center, New York, NY

9/2008 – 8/2015      Pathologist-in-Chief, University of Alabama Hospital, Birmingham, AL

9/2008 – 8/2015      Chair, Department of Pathology, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL

7/2002 – 6/2013      Veteran’s Administration Medical Center of Birmingham, AL

7/2002 – 8/2008      Professor and Director, Division of Neuropathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL

7/2001 – 6/2002      Professor, Division of Neuropathology, Department of Pathology and Immunology, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO

7/1994 – 6/2001      Associate Professor, Division of Neuropathology, Department of Pathology and Immunology, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO

7/1989 – 6/1994      Assistant Professor, Division of Neuropathology, Department of Pathology and Immunology, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO

Presentations

National:

European Neuromuscular Center Workshop on Quality in Translational Research (February 10-11, 2017)

Cold Spring Harbor, NY – Banbury Conference on Evolution and Revolution in Anatomic Pathology (December 4-7, 2016)

Genetech, San Francisco – “Pathology in the Era of Precision Medicine: A Discipline in Transition”

(09-27-16)

Columbia University, New York – "Molecular Pathways and Therapeutic Potential of Autophagic Stress-Induced Malignant Glial Tumor Cell Death" (04-02-15)

University of California, San Diego - “Autophagy Targeted Therapy for Malignant Glial Neoplasms” (4-29-14)

Duke University – “Autophagy Targeted Therapies for Malignant Glial Neoplasms”. (3-21-14)

Temple University – “Autophagy Targeted Therapies for Malignant Glial Neoplasms”. (11-15-13)

UAB – Southeastern Medical Scientists Symposium – “Scientific Currency: The changing Landscape of Publishing” Session Leader (10-26-13)

APSA – “Men in Science” (10-14-13)

SEAPC – “NIH Funding Withdrawal, Where’s the Fix?” (10-4-13)

Experimental Biology 2013 Meeting – “Dancing with Journals” (4-29-13)

UAB Genetics and Genomics Seminar Series “Lysosomotropic Therapy for Malignant Glial Neoplasms” (5-18-12)

University of Pittsburgh – “Lysosomotropic Therapy for Malignant Glial Neoplasms” (5-9-12)

Case Western Reserve University – “Lysosomotropic Therapy for Malignant Glial Neoplasms” (4-9-12)

University of Washington “Apoptosis and Autophagy:  Key Partners in Neuronal Cell Death Regulation” (3-29-12)

Indiana University - Guest Speaker of the Gregory Derringer Grand Rounds – “Apoptosis and Autophagy:  Neuropathology in the Balance” (5-5-11)

International:

The Netherlands – European Neuromuscular Center Workshop on Quality in Translational Research (February 10-11, 2017)

Italian Pathology Society (SIPMET) Annual Meeting; Palermo, Italy – Plenary Lecture – “Autophagy Targeted Therapy for Malignant Glial Neoplasms” (9-17-14)

ICHC 2012 Meeting, Kyoto, Japan – “Autophagy Targeted Therapeutics for Malignant Glial Neoplasms” (8-27-12)

Juntendo University; Tokyo, Japan – “Molecular Regulation of Neural Stem Cell Death” (7-4-09)

Nihon University School of Medicine; Tokyo, Japan – “Apoptosis, Autophagy and the Brain:  A Delicate Balance Between Neuroprotection and Neuropathology” (7-3-09)

ICHC, Gdansk Poland; “Measuring Journal Success – IF Alternatives” (8-25-08)

ICHC, Gdansk Poland; “Sensitive and Stable Immunohistochemical Detection” (8-24-08)

Osaka University, Japan “Beyond Programmed Cell Death: Novel Neuronal Death Pathways” (9-8-06)

16th International Microscopy Congress, Sapporo, Japan, “Characterization of p53-Dependent Neural Stem Cell Death Pathways” (9-5-06)

16th International Congress of the International Federation of Association of Anatomists (IFAA), Kyoto, Japan, “Bcl-2 and Caspase Regulation of Neural Precursor Cell Death” (8-26-04)

RIKEN Developmental Biology Center, Kobe, Japan, “Bcl-2 and Caspase Regulation of Neuronal Cell Death and Degeneration-Lessons from Gene-Disrupted Mice” (8-24-04)

Pharmacology 2001, Vancouver, CA; “Antibodies and Tyramide Signal Amplification” (3-29-01)

Patents

Barchas JD, Weber E, Evans CJ, Chang JK, Lorenz RG, Roth KA:  Gastrin releasing peptide-like peptides.  US Patent Number:  4,613,586     Issued:  September 23, 1986.

Roth KA and Lorenz R:  Method for localization and quantitation of a substance in a biological sample.  US Patent Number:  5,902,727     Issued:  May 11, 1999.  WIPO Number:  1998010290  Issued:  March 13, 1998.  EPO Number:  1023604  Issued:  August 2, 2000. 

Bobrow MN and Roth KA:  4-(4-Hydroxystyryl) Pyridine-containing substrates for an analyte dependent enzyme activation system.  US Patent Serial Number 6,355,443 B1     Issued:  March 12, 2002.  WIPO Number:  2000055358   Issued:  September 22, 2000. 

Bobrow MN, Adler KE, Roth KA:  Enhanced catalyzed reporter deposition.  US Patent Serial Number 6,372,937 B1.   Issued:  April 16, 2002.

Bobrow MN and Roth KA:  A method of permanent fluorescent assay.  US Patent Serial Number 6,518,036 B1.   Issued:  February 11, 2003.  WIPO Number:  2000055115  Issued:  September 22, 2000. 

Bobrow MN, Adler KE, Roth KA:  Enhanced catalyzed reporter deposition.  US Patent Serial Number 6,593,100 B2.   Issued:  July 15, 2003.  WIPO Number:  2000028077  Issued:  May 19, 2000.  EPO Number:  1129214  Issued:  February 2, 2005. 

Shacka J, Roth KA:  Prevention of Neurodegeneration by Macrolide Antibiotics.  WIPO Number:  2007022076  Issued:  February 23, 2007.  EPO Number:  1921915.  Issued:  May 21, 2008. 

Committees/Societies/Memberships

American Association of Neuropathologists

American Association of University Pathologists - Pluto Club

American Society for Investigative Pathology

Association of Pathology Chairs

Histochemical Society

Society for Neuroscience

United States and Canadian Academy of Pathology

Honors & Awards

1979                                             Graduated with highest honors, University of Michigan

1982-1985                                  Medical Scientist Training Program Fellow, Stanford University

1989-1992                                  Lucille P. Markey Charitable Trust, New Faculty Recruitment

                                                      Award, Washington University School of Medicine

1992,93,94                                 Selected Lecturer of the Year by the Washington University Medical School

                                                      Classes of 1994, 1995, and 1996

1992,93,94,95,96,97,98         Distinguished Teaching Service Awards, Washington University School of Medicine

1995                                             Weil Award for the best paper on experimental neuropathology, Annual

                                      Meeting of the American Assoc. of Neuropathologists

1998                                             Weil Award, Honorable Mention, Annual Meeting of the Amer. Assoc. of Neuropathologists

2001                                             Rubinstein Award, Honorable Mention, Best Paper on Neuro-Oncology;

                                                      Annual Meeting of the American Association of Neuropathologists

2005                                             Erie County Chamber of Commerce (OH) – Gallery of Achievers

2007                                             Elected Member, American Association of University Pathologists – Pluto Club

2008                                             Appointed to the Robert and Ruth Anderson Endowed Chair in Pathology

2009                                             Sandusky St. Mary’s Central Catholic High School, Hall of Fame; Professional Achievement

2011                                             Carpenter-Rasch Award – Acknowledgement of Contributions to the Histochemical Society

Research Interests

  • Neurotransmitter and Neurotrophin Receptors and Cell Signaling
  • CNS Cancer Biology and Treatment

Publications

Kaza N, Kohli L, Graham CD, Klocke BJ, Carroll SL, and Roth KA. BNIP3 regulates AT101 [(-)-Gossypol] induced death in Malignant Peripheral Nerve Sheath Tumor Cells. PLoS One. 2014 May 13;9(5):e96733. eCollection 2014. PMCID: PMC4019476.

Brosius SN, Turk AN, Byer SJ, Brossier NM, Kohli L, Whitmire A, Mikhail FM, Roth KA, Carroll SL. Neuregulin-1 Overexpression and TRP53 Haploinsufficiency Cooperatively Promote de novo Malignant Peripheral Nerve Sheath Tumor Pathogenesis. Acta Neuropathol. 2014 Apr;127(4):573-91. PMCID: PMC3999224.

Kohli L, Kaza N, Coric T, Byer SJ, Borssier NM, Klocke BJ, Bjornsti MA, Carroll SL, Roth KA. 4-Hydroxy Tamoxifen Induces Autophagic Death through K-Ras Degradation. Cancer Research, 73(14) July 15, 2013: 4395-4405. PMCID: PMC3715566.

Ghosh AP, Klocke BJ, Ballestas ME, Roth KA: CHOP Potentially Co-Operates with FOXO3a in Neuronal Cells to Regulate PUMA and BIM Expression in Response to ER Stress. PLoS One; 2012; 7(6):e39586. epub 2012 June 28. PMCID: PMC3386252.

Kohli L, Kaza N. Lavalley NJ, Turner KL, Byer S, Carroll SL, Roth KA: The pan erbB Inhibitor PD168393 Enhances Lysosomal Dysfunction-Induced Apoptotic Death in Malignant Peripheral Nerve Sheath Tumor Cells. Neuro-Oncology, 2012; 14(3):266-277. PMCID: PMC3280808.

Kaza N, Kohli L, Roth KA: Autophagy in Brain Tumors: A New Target for Therapeutic Intervention. Brain Pathol. 2012; 22:89-98. PMCID: PMC3243074.

Geng Y, Kohli L, Klocke BJ, Roth KA: Chloroquine-Induced Autophagic Vacuole Accumulation and Cell Death in Glioma Cells is p53 Independent. Neuro-Oncology 2010; 12(5):473-481. PMCID: PMC2940627.

Walls KC, Ghosh AP, Ballestas ME, Klocke BJ, Roth KA: bcl-2/Adenovirus E1B 19-kd Interacting Protein 3 (BNIP3) Regulates Hypoxia-Induced Neural Precursor Cell Death. J Neuropathol Exp Neurol 2009 68:1326-38. PMCID: PMC2791349.

Walls KC, Ghosh AP, Franklin AL, Klocke BJ, Ballestas M, Shacka JJ, Zhang J, Roth KA: Lysosome Dysfunction Triggers Atg7-Dependent Neural Apoptosis. J. Biol. Chem. 2010; 285(14):10497-10507. PMCID: PMC2856257.

Geng Y, Walls KC, Ghosh AP, Akhtar RS, Klocke BJ, Roth KA: Cytoplasmic p53 and Activated Bax Regulate p53-Dependent, Transcription-Independent Neural Precursor Cell Apoptosis. J Histochem Cytochem 2010; 58 (3): 265-275. PMCID: PMC2825492.