Research Summary

I am widely recognized for my expertise in autophagy, a tightly regulated cellular self-digestion process, and how this process regulates epithelial cell fate, oncogenic transformation, and carcinoma progression. I am a board-certified pathologist and completed post-doctoral training with Dr. Joan Brugge (Harvard Medical School), where I became known for my studies of oncogene regulation of cell death using three-dimensional (3D) organotypic culture systems. Since becoming faculty at UCSF in 2005, I have focused on the regulation of autophagy in cancer, publishing over 65 papers and invited reviews and receiving multiple extramural grants from the NCI, DOD, and private foundations. My laboratory pursues two broad goals: (1) to delineate the multifaceted roles of autophagy in adhesion independent survival and transformation in vitro, as well as on cancer progression and metastatic disease in vivo; and (2) to dissect the biochemical and in vivo physiological functions of the molecules that control autophagy (called ATGs) to ultimately exploit this process for therapeutic benefit.

Research Funding

  • December 13, 2017 - November 30, 2022 - Stromal Fibroblast Autophagy In Tumor Progression and Desmoplasia, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA213775
  • September 15, 2017 - May 31, 2022 - Autophagy-dependent exosome loading and biogenesis in AD and FTD, Co-Principal Investigator. Sponsor: NIH/NIA, Sponsor Award ID: R01AG057462
  • September 1, 2014 - August 31, 2019 - Autophagy as a microenvironmental regulator of tumorigenesis and resistance, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA188404
  • June 1, 2016 - May 31, 2018 - Deciphering Autophagy-Dependent Secretion In Cancer Via Proximity-Based Biotinylation, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R21CA201849

Education

Georgia Institute of Technology, Atlanta, Georgia, 1988-1992, Bachelor of Science in Chemistry, Highest Honors
Harvard Medical School, Boston, Massachusetts, 1992-1998, Doctor of Medicine, magna cum laude
National Cancer Institute, Bethesda, MD, NIH-HHMI Scholar, 1995-1997, Biochemistry
Resident, Anatomic Pathology, Department of Pathology, Brigham and Women's Hospital, 1998-2000
Clinical Fellow, Department of Pathology, Brigham and Women's Hospital, 2000-2003
Postdoctoral Fellow, Department of Cell Biology, Harvard Medical School, 2000-2005

Honors & Awards

  • 2006
    Charles Culpeper Scholarship in the Medical Sciences, Partnership For Cures
  • 2006
    AACR Genentech Bio-Oncology Career Development Award
  • 2006
    Howard Hughes Medical Institute Early Career Award For Physician Scientists
  • 2011-2016
    DOD Breast Cancer Research Program Era of Hope Scholar Award
  • 2013
    Elected Member, American Society of Clinical Investigation
  • 2016
    Keith Porter Fellow for Excellence in Cell Biology, American Society for Cell Biology
  • 2019
    Ramzi S. Cotran Visiting Professor, Brigham and Women’s Hospital, Harvard Medical School
  • 2021
    Outstanding Investigator Award, American Society of Investigative Pathology

Selected Publications

  1. Beyond Autophagy: The Expanding Roles of ATG8 Proteins.  View on PubMed
  2. Marsh T, Tolani B, Debnath J The pleiotropic functions of autophagy in metastasis.  View on PubMed
  3. Nguyen TA, Debnath J Unconventional secretion: cargo channeling by TMED10.  View on PubMed
  4. Zhang J, Velmeshev D, Hashimoto K, Huang YH, Hofmann JW, Shi X, Chen J, Leidal AM, Dishart JG, Cahill MK, Kelley KW, Liddelow SA, Seeley WW, Miller BL, Walther TC, Farese RV, Taylor JP, Ullian EM, Huang B, Debnath J, Wittmann T, Kriegstein AR, Huang EJ Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency.  View on PubMed
  5. Goldsmith J, Marsh T, Asthana S, Leidal AM, Suresh D, Olshen A, Debnath J Ribosome profiling reveals a functional role for autophagy in mRNA translational control.  View on PubMed
  6. Leidal AM, Debnath J LC3-dependent extracellular vesicle loading and secretion (LDELS).  View on PubMed
  7. Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, Sohn ASW, Mukhopadhyay S, Lin EY, Parker SJ, Banh RS, Paulo JA, Wen KW, Debnath J, Kim GE, Mancias JD, Fearon DT, Perera RM, Kimmelman AC Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.  View on PubMed
  8. Marsh T, Debnath J Autophagy suppresses breast cancer metastasis by degrading NBR1.  View on PubMed
  9. Marsh T, Kenific CM, Suresh D, Gonzalez H, Shamir ER, Mei W, Tankka A, Leidal AM, Kalavacherla S, Woo K, Werb Z, Debnath J Autophagic Degradation of NBR1 Restricts Metastatic Outgrowth during Mammary Tumor Progression.  View on PubMed
  10. Leidal AM, Debnath J Unraveling the mechanisms that specify molecules for secretion in extracellular vesicles.  View on PubMed
  11. Leidal AM, Huang HH, Marsh T, Solvik T, Zhang D, Ye J, Kai F, Goldsmith J, Liu JY, Huang YH, Monkkonen T, Vlahakis A, Huang EJ, Goodarzi H, Yu L, Wiita AP, Debnath J The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles.  View on PubMed
  12. Amaravadi RK, Kimmelman AC, Debnath J Targeting Autophagy in Cancer: Recent Advances and Future Directions.  View on PubMed
  13. Tan JMJ, Mellouk N, Osborne SE, Ammendolia DA, Dyer DN, Li R, Brunen D, van Rijn JM, Huang J, Czuczman MA, Cemma MA, Won AM, Yip CM, Xavier RJ, MacDuff DA, Reggiori F, Debnath J, Yoshimori T, Kim PK, Fairn GD, Coyaud E, Raught B, Muise AM, Higgins DE, Brumell JH An ATG16L1-dependent pathway promotes plasma membrane repair and limits Listeria monocytogenes cell-to-cell spread.  View on PubMed
  14. Leidal AM, Levine B, Debnath J Autophagy and the cell biology of age-related disease.  View on PubMed
  15. Marsh T, Debnath J WIPIng the Brakes off Autophagy Induction.  View on PubMed
  16. Chen SH, Jang GM, Hüttenhain R, Gordon DE, Du D, Newton BW, Johnson JR, Hiatt J, Hultquist JF, Johnson TL, Liu YL, Burton LA, Ye J, Reichermeier KM, Stroud RM, Marson A, Debnath J, Gross JD, Krogan NJ CRL4AMBRA1 targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.  View on PubMed
  17. Commisso C, Debnath J Macropinocytosis Fuels Prostate Cancer.  View on PubMed
  18. Murrow L, Debnath J Atg12-Atg3 Coordinates Basal Autophagy, Endolysosomal Trafficking, and Exosome Release.  View on PubMed
  19. Cadwell K, Debnath J Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins.  View on PubMed
  20. Roy S, Debnath J Autophagy enables retromer-dependent plasma membrane translocation of SLC2A1/GLUT1 to enhance glucose uptake.  View on PubMed

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