Schwartz, Alan L., Ph.D., M.D.  schwartz@wustl.edu

Professor of Pediatrics, Hematology and Oncology
Professor of Developmental Biology
Developmental BiologyHematology and Oncology

phone: (314) 454-6018

Research Interests

Dr. Schwartz's laboratory is focused on the cell and molecular biology of intracellular protein targeting and degradation. Specifically, his laboratory has defined two areas of concentration, which are closely integrated. The first area of focus is understanding the role of protein processing and degradation within the endosomal/lysosomal pathway and in the cytoplasm. The lysosomal pathway is responsible for degradation of extracellular proteins. Within the cytoplasm the major (and best understood) proteolytic system is the ubiquitin-proteasome system. This pathway involves dozens of distinct components and is involved in the degradation of short lived and abnormal proteins. Using eukaryotic mutants of the pathway and specific antibodies to components of the pathway, the Schwartz laboratory identified a linkage between these two systems. Furthermore, using in vitro reconstituted systems they have begun to dissect the structural elements of substrates (including oncoproteins) which signal their processing and degradation. Our recent focus is on the role of the ubiquitin-proteasome in transcription factor (e.g., MyoD, E2A) degradation in the cytoplasm and nucleus and the molecular mechanisms involved. The second area is the cell and molecular biology of receptor-mediated endocytosis and its regulation. The Schwartz research group has identified a huge, multifunctional cell surface endocytosis receptor (LRP) which governs the plasma clearance of several physiologically important ligands including the plasminogen activators t-PA and u-PA, as well as apolipoprotein E, lipoprotein lipase and most recently TFPI (tissue factor pathway inhibitor), a regulator of blood coagulation. Our approaches include immuno-electron microscopy as well as in vivo gene targeting. Recent focus is directed to regulation of LRP and ligand trafficking and turnover.

Education

  • BA, Case Western Reserve University1970
  • PhD, Case Western Reserve University1974
  • MD, Case Western Reserve University1976

Training

  • Research Fellow, University of Helsinki1972 - 1973
  • NIH Postdoctoral Fellow, Case Western Reserve University1974 - 1974
  • Fellow of the Medical Research Council of New Zealand, University of Auckland, National Women's Hospital1975 - 1976
  • Residency, Children's Hospital Medical Center1976 - 1978
  • Clinical Fellow in Pediatrics, Harvard Medical School1977 - 1978
  • Fellow in Hematology/Oncology, Children's Hospital Medical Center and the Dana Farber Cancer Institute1978 - 1979

Licensure and Board Certification

  • MA, Medical License 1977
  • Diplomate of the American Board of Pediatrics 1981
  • MO, Medical License 1986

Honors

  • University Book Prize in Biology, Case Western Reserve University1970
  • Alpha Omega Alpha, Case Western Reserve University School of Medicine1975
  • John L. Caughey, M.D. Award for Clinical Investigation, Case Western Reserve University School of Medicine1975
  • Bronze Medal of the Royal Humane Society of New Zealand1976
  • Upjohn Award in Clinical Pharmacology, Case Western Reserve University School of Medicine1976
  • George von L. Meyer Award, Children's Hospital Medical Center1977
  • Sidney Farber House Staff Prize, Children's Hospital Medical Center1978
  • David Abraham Fellowship in Pediatric Hematology and Oncology1979
  • Bushrod H. Campbell and Adah F. Hall Medical Foundation Fellow1980 - 1982
  • Outstanding Young Investigator, Boston Blood Club1981
  • John A. and George Hartford Foundation Fellow1982 - 1985
  • Society for Pediatric Research, Young Investigator Award1983
  • Established Investigator, American Heart Association1985 - 1990
  • Alumni Endowed Professor of Pediatrics, Washington University School of Medicine1987 - 1998
  • Gold Metal Award, Hospital Association of Greater St. Louis1988
  • Teacher of the Year, Washington University School of Medicine1988
  • Basil O'Connor Award, March of Dimes1990 - 1995
  • Outstanding Clinical Teacher 1990-1991, St. Louis Children's Hospital1991
  • Distinguished Visiting Professor, University of Utrecht School of Medicine, Utrecht, The Netherlands1993 - 1998
  • E. Mead Johnson Award1993
  • Distinguished Service Teaching Award, Washington University School of Medicine1993
  • Who's Who in Midwest1994 - 2002
  • Distinguished Service Teaching Award, Washington University School of Medicine1994
  • Harriet B. Spoehrer Professor of Pediatrics, Washington University School of Medicine1995 - 2016
  • Who's Who in American Education1995 - Pres
  • United States Patent 5,474,766 for Methods and Compositions for Inhibition of Hepatic Clearance of Tissue Type Plasminogen Activator, Docket Number C00108/059407 (issued December 12)1995
  • Who's Who in America1996 - 2010
  • Fellows Award, Barnes-Jewish Hospital Foundation1996
  • United States Patent 5,650,391 for Methods and Compositions for Inhibition of Hepatic Clearance of Tissue Factor Pathway Inhibitor (issued July 22)1997
  • Elected to National Academy of Medicine (Formally Institute of Medicine, National Academy of Sciences, U.S.A.)1999 - Pres
  • Who's Who in Medicine and Healthcare2001 - Pres
  • Best Doctors in America2003 - 2010
  • American Men and Women of Science2004
  • Who's Who Among America's Teachers2004 - Pres
  • Distinguished Faculty Award, Washington University School of Medicine2006
  • Elected Fellow, American Association for the Advancement of Science2007 - Pres
  • Best Doctors in America2007 - 2010
  • Fellows Award, Academy of Science – St. Louis2010
  • Doctor Medicinae et Chirurgiae Honoris Causa, University of Helsinki, Finland (Honorary Degree)2010

Selected Publications view all (229)


Publication Co-Authors

1.
Isoform-specific SCF(Fbw7) ubiquitination mediates differential regulation of PGC-1α. J Cell Physiol. 2015;230(4):842-52. doi:10.1002/jcp.24812  PMCID:PMC4596538  PMID:25204433 
2.
American Pediatric Society 2014 presidential address: the thrill of discovery (and other foundations of biomedical research). Pediatr Res. 2014;76(3):316-20. doi:10.1038/pr.2014.81  PMID:24937547 
3.
Commentary: physician-scientist attrition: stemming the tide through national networks for training and development. Acad Med. 2011;86(9):1071-2. doi:10.1097/ACM.0b013e318224fd75  PMID:21865903 
4.
The Future of Children's Health in the Genomic Era. Rambam Maimonides Med J. 2011;2(3):e0053. doi:10.5041/RMMJ.10053  PMCID:PMC3678796  PMID:23908811 
5.
Ubiquitin proteasome-dependent degradation of the transcriptional coactivator PGC-1{alpha} via the N-terminal pathway. J Biol Chem. 2010;285(51):40192-200. doi:10.1074/jbc.M110.131615  PMCID:PMC3001001  PMID:20713359 
6.
Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9. Cancer Res. 2009;69(3):879-86. doi:10.1158/0008-5472.CAN-08-3379  PMCID:PMC2633434  PMID:19176371 
7.
Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu Rev Pharmacol Toxicol. 2009;49:73-96. doi:10.1146/annurev.pharmtox.051208.165340  PMID:18834306 
8.
The N-terminal domain of MyoD is necessary and sufficient for its nuclear localization-dependent degradation by the ubiquitin system. Proc Natl Acad Sci U S A. 2008;105(41):15690-5. doi:10.1073/pnas.0808373105  PMCID:PMC2560994  PMID:18836078 
9.
In vivo interactions of MyoD, Id1, and E2A proteins determined by acceptor photobleaching fluorescence resonance energy transfer. FASEB J. 2008;22(6):1694-701. doi:10.1096/fj.07-095000  PMID:18198216 
10.
Glucocorticoids differentially regulate degradation of MyoD and Id1 by N-terminal ubiquitination to promote muscle protein catabolism. Proc Natl Acad Sci U S A. 2008;105(9):3339-44. doi:10.1073/pnas.0800165105  PMCID:PMC2265166  PMID:18296633 
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