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

  • June 1, 2007 - January 31, 2026 - Autophagy and Pro-metastatic Differentiation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA126792
  • December 13, 2017 - November 30, 2022 - Stromal Fibroblast Autophagy In Tumor Progression and Desmoplasia , Principal Investigator . Sponsor: NIH, 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, Sponsor Award ID: R01AG057462
  • September 1, 2014 - August 31, 2020 - Autophagy as a microenvironmental regulator of tumorigenesis and resistance , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA188404

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. Yang Y, Gomez M, Marsh T, Poillet-Perez L, Sawant A, Chen L, Park NR, Jackson SR, Hu Z, Alon N, Liu C, Debnath J, Guan JL, Davidson S, Verzi M, White E. Autophagy in PDGFRa+ mesenchymal cells is essential for intestinal stem cell survival. Proc Natl Acad Sci U S A. 2022 May 24; 119(21):e2202016119.  View on PubMed
  2. Solvik TA, Nguyen TA, Tony Lin YH, Marsh T, Huang EJ, Wiita AP, Debnath J, Leidal AM. Secretory autophagy maintains proteostasis upon lysosome inhibition. J Cell Biol. 2022 Jun 06; 221(6).  View on PubMed
  3. AACR Pathology Task Force. Pathology: Hub and Integrator of Modern, Multidisciplinary [Precision] Oncology. Clin Cancer Res. 2022 01 15; 28(2):265-270.  View on PubMed
  4. Liu JY, Lin YT, Leidal AM, Huang HH, Ye J, Wiita AP, Debnath J. GRASP55 restricts early-stage autophagy and regulates spatial organization of the early secretory network. Biol Open. 2021 10 15; 10(10).  View on PubMed
  5. Rudnick JA, Debnath J. Autophagy in host stromal fibroblasts supports tumor desmoplasia. Autophagy. 2021 12; 17(12):4497-4498.  View on PubMed
  6. Li H, Doric Z, Berthet A, Jorgens DM, Nguyen MK, Hsieh I, Margulis J, Fang R, Debnath J, Sesaki H, Finkbeiner S, Huang E, Nakamura K. Longitudinal tracking of neuronal mitochondria delineates PINK1/Parkin-dependent mechanisms of mitochondrial recycling and degradation. Sci Adv. 2021 Aug; 7(32).  View on PubMed
  7. Rudnick JA, Monkkonen T, Mar FA, Barnes JM, Starobinets H, Goldsmith J, Roy S, Bustamante Eguiguren S, Weaver VM, Debnath J. Autophagy in stromal fibroblasts promotes tumor desmoplasia and mammary tumorigenesis. Genes Dev. 2021 07 01; 35(13-14):963-975.  View on PubMed
  8. Kaur J, Goldsmith J, Tankka A, Bustamante Eguiguren S, Gimenez AA, Vick L, Debnath J, Vlahakis A. Atg32-dependent mitophagy sustains spermidine and nitric oxide required for heat-stress tolerance in Saccharomycescerevisiae. J Cell Sci. 2021 06 01; 134(11).  View on PubMed
  9. Kaur J, Goldsmith J, Tankka A, Eguiguren SB, Gimenez AA, Vick L, Debnath J, Vlahakis A. Atg32 dependent mitophagy sustains spermidine and nitric oxide required for heat stress tolerance in S. cerevisiae. J Cell Sci. 2021 May 26.  View on PubMed
  10. Mondal G, Debnath J. NRF2 activates macropinocytosis upon autophagy inhibition. Cancer Cell. 2021 05 10; 39(5):596-598.  View on PubMed
  11. Tulpule A, Guan J, Neel DS, Allegakoen HR, Lin YP, Brown D, Chou YT, Heslin A, Chatterjee N, Perati S, Menon S, Nguyen TA, Debnath J, Ramirez AD, Shi X, Yang B, Feng S, Makhija S, Huang B, Bivona TG. Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules. Cell. 2021 05 13; 184(10):2649-2664.e18.  View on PubMed
  12. Leidal AM, Debnath J. Emerging roles for the autophagy machinery in extracellular vesicle biogenesis and secretion. FASEB Bioadv. 2021 May; 3(5):377-386.  View on PubMed
  13. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, Adamopoulos IE, Adeli K, Adolph TE, Adornetto A, Aflaki E, Agam G, Agarwal A, Aggarwal BB, Agnello M, Agostinis P, Agrewala JN, Agrotis A, Aguilar PV, Ahmad ST, Ahmed ZM, Ahumada-Castro U, Aits S, Aizawa S, Akkoc Y, Akoumianaki T, Akpinar HA, Al-Abd AM, Al-Akra L, Al-Gharaibeh A, Alaoui-Jamali MA, Alberti S, Alcocer-Gómez E, Alessandri C, Ali M, Alim Al-Bari MA, Aliwaini S, Alizadeh J, Almacellas E, Almasan A, Alonso A, Alonso GD, Altan-Bonnet N, Altieri DC, Álvarez ÉMC, Alves S, Alves da Costa C, Alzaharna MM, Amadio M, Amantini C, Amaral C, Ambrosio S, Amer AO, Ammanathan V, An Z, Andersen SU, Andrabi SA, Andrade-Silva M, Andres AM, Angelini S, Ann D, Anozie UC, Ansari MY, Antas P, Antebi A, Antón Z, Anwar T, Apetoh L, Apostolova N, Araki T, Araki Y, Arasaki K, Araújo WL, Araya J, Arden C, Arévalo MA, Arguelles S, Arias E, Arikkath J, Arimoto H, Ariosa AR, Armstrong-James D, Arnauné-Pelloquin L, Aroca A, Arroyo DS, Arsov I, Artero R, Asaro DML, Aschner M, Ashrafizadeh M, Ashur-Fabian O, Atanasov AG, Au AK, Auberger P, Auner HW, Aurelian L, Autelli R, Avagliano L, Ávalos Y, Aveic S, Aveleira CA, Avin-Wittenberg T, Aydin Y, Ayton S, Ayyadevara S, Azzopardi M, Baba M, Backer JM, Backues SK, Bae DH, Bae ON, Bae SH, Baehrecke EH, Baek A, Baek SH, Baek SH, Bagetta G, Bagniewska-Zadworna A, Bai H, Bai J, Bai X, Bai Y, Bairagi N, Baksi S, Balbi T, Baldari CT, Balduini W, Ballabio A, Ballester M, Balazadeh S, Balzan R, Bandopadhyay R, Banerjee S, Banerjee S, Bánréti Á, Bao Y, Baptista MS, Baracca A, Barbati C, Bargiela A, Barilà D, Barlow PG, Barmada SJ, Barreiro E, Barreto GE, Bartek J, Bartel B, Bartolome A, Barve GR, Basagoudanavar SH, Bassham DC, Bast RC, Basu A, Batoko H, Batten I, Baulieu EE, Baumgarner BL, Bayry J, Beale R, Beau I, Beaumatin F, Bechara LRG, Beck GR, Beers MF, Begun J, Behrends C, Behrens GMN, Bei R, Bejarano E, Bel S, Behl C, Belaid A, Belgareh-Touzé N, Bellarosa C, Belleudi F, Belló Pérez M, Bello-Morales R, Beltran JSO, Beltran S, Benbrook DM, Bendorius M, Benitez BA, Benito-Cuesta I, Bensalem J, Berchtold MW, Berezowska S, Bergamaschi D, Bergami M, Bergmann A, Berliocchi L, Berlioz-Torrent C, Bernard A, Berthoux L, Besirli CG, Besteiro S, Betin VM, Beyaert R, Bezbradica JS, Bhaskar K, Bhatia-Kissova I, Bhattacharya R, Bhattacharya S, Bhattacharyya S, Bhuiyan MS, Bhutia SK, Bi L, Bi X, Biden TJ, Bijian K, Billes VA, Binart N, Bincoletto C, Birgisdottir AB, Bjorkoy G, Blanco G, Blas-Garcia A, Blasiak J, Blomgran R, Blomgren K, Blum JS, Boada-Romero E, Boban M, Boesze-Battaglia K, Boeuf P, Boland B, Bomont P, Bonaldo P, Bonam SR, Bonfili L, Bonifacino JS, Boone BA, Bootman MD, Bordi M, Borner C, Bornhauser BC, Borthakur G, Bosch J, Bose S, Botana LM, Botas J, Boulanger CM, Boulton ME, Bourdenx M, Bourgeois B, Bourke NM, Bousquet G, Boya P, Bozhkov PV, Bozi LHM, Bozkurt TO, Brackney DE, Brandts CH, Braun RJ, Braus GH, Bravo-Sagua R, Bravo-San Pedro JM, Brest P, Bringer MA, Briones-Herrera A, Broaddus VC, Brodersen P, Brodsky JL, Brody SL, Bronson PG, Bronstein JM, Brown CN, Brown RE, Brum PC, Brumell JH, Brunetti-Pierri N, Bruno D, Bryson-Richardson RJ, Bucci C, Buchrieser C, Bueno M, Buitrago-Molina LE, Buraschi S, Buch S, Buchan JR, Buckingham EM, Budak H, Budini M, Bultynck G, Burada F, Burgoyne JR, Burón MI, Bustos V, Büttner S, Butturini E, Byrd A, Cabas I, Cabrera-Benitez S, Cadwell K, Cai J, Cai L, Cai Q, Cairó M, Calbet JA, Caldwell GA, Caldwell KA, Call JA, Calvani R, Calvo AC, Calvo-Rubio Barrera M, Camara NO, Camonis JH, Camougrand N, Campanella M, Campbell EM, Campbell-Valois FX, Campello S, Campesi I, Campos JC, Camuzard O, Cancino J, Candido de Almeida D, Canesi L, Caniggia I, Canonico B, Cantí C, Cao B, Caraglia M, Caramés B, Carchman EH, Cardenal-Muñoz E, Cardenas C, Cardenas L, Cardoso SM, Carew JS, Carle GF, Carleton G, Carloni S, Carmona-Gutierrez D, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy. 2021 Jan; 17(1):1-382.  View on PubMed
  14. Nieto-Torres JL, Leidal AM, Debnath J, Hansen M. Beyond Autophagy: The Expanding Roles of ATG8 Proteins. Trends Biochem Sci. 2021 08; 46(8):673-686.  View on PubMed
  15. Marsh T, Tolani B, Debnath J. The pleiotropic functions of autophagy in metastasis. J Cell Sci. 2021 01 22; 134(2).  View on PubMed
  16. Marsh T, Tolani B, Debnath J. The pleiotropic functions of autophagy in metastasis. J Cell Sci. 2021 01 15; 134(2).  View on PubMed
  17. Nguyen TA, Debnath J. Unconventional secretion: cargo channeling by TMED10. Cell Res. 2020 09; 30(9):713-714.  View on PubMed
  18. 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. Nature. 2020 12; 588(7838):459-465.  View on PubMed
  19. 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. Commun Biol. 2020 07 17; 3(1):388.  View on PubMed
  20. Leidal AM, Debnath J. LC3-dependent extracellular vesicle loading and secretion (LDELS). Autophagy. 2020 06; 16(6):1162-1163.  View on PubMed

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