The study of autophagy (= “self-eating”) has generated tremendous attention due to the recognition that autophagy is involved in multiple developmental processes and various human diseases including cancer.
Autophagy is a catabolic cellular process that provides nutrients and energy through lysosomal degradation of cytoplasmic components engulfed in double membrane-bound vesicles known as autophagosomes. Autophagy occurs at basal rates in virtually all eukaryotic cells to fulfill homeostatic functions such as the recycling of long-lived proteins and damaged organelles. In this way, autophagy acts to safeguard genome integrity and suppress tumorigenesis. Under cellular stress conditions, autophagy is upregulated as an adaptive survival response. Cancer cells may exploit elevated autophagy to survive low nutrient conditions, fuel proliferation, and escape the effects of chemotherapy and other treatments. Consequently, autophagy is under investigation as a target for anticancer therapy in preclinical studies and clinical trials. However, our understanding of the mechanisms by which cells utilize the autophagy pathway to promote both normal development and cancer progression is limited.
To help elucidate these mechanisms, the overall goals of my research program are to identify and characterize regulators of autophagy, investigate the roles of autophagy during normal development, and evaluate the therapeutic potential of autophagy modulation for cancer treatment.
For more information, visit our research lab website.
- Bosc D, Vezenkov L, Bortnik S, An J, Xu J, Choutka C, Hannigan AM, Kovacic S, Loo S, Clark PGK, Chen G, Guay-Ross RN, Yang K, Dragowska WH, Zhang F, Go NE, Leung A, Honson NS, Pfeifer TA, Gleave M, Bally M, Jones SJ, Gorski SM, Young RN. A new quinoline-based chemical probe inhibits the autophagy-related cysteine protease ATG4B. Scientific Reports. 2018; 8(1):11653. PMID: 30076329
- Xu J, Camfield R, Gorski SM. The interplay between exosomes and autophagy - partners in crime. Journal of Cell Science. 2018; 131(15). PMID: 30076239
- Choutka C, DeVorkin L, Go NE, Hou YC, Moradian A, Morin GB, Gorski SM. Hsp83 loss suppresses proteasomal activity resulting in an upregulation of caspase-dependent compensatory autophagy. Autophagy. 2017; 13(9):1573-1589. PMID: 28806103
- Bortnik S, Choutka C, Horlings HM, Leung S, Baker JH, Lebovitz C, Dragowska WH, Go NE, Bally MB, Minchinton AI, Gelmon KA, Gorski SM. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition. Oncotarget. 2016; 7(41):66970-66988. PMID: 27556700