Amaravadi Lab

Ravi Amaravadi, MD
PI
 ravi.amaravadi@pennmedicine.upenn.edu

Dr. Amaravadi is a physician scientist with expertise in autophagy, conducting early phase clinical trials, and clinically treating patients with advanced melanoma. He was one of the first to demonstrate that autophagy is a targetable mechanism of resistance in cancer therapy using animal models. He has translated this finding into numerous phase I/II clinical trials testing hydroxychloroquine (HCQ) as a possible autophagy inhibitor and anticancer agent in multiple cancers. These translational studies were the first attempt to modulate autophagy therapeutically in any disease. His laboratory published the first evidence that autophagy is elevated in melanoma patient tumors and predicts poor survival. His work on the role of autophagy in melanoma has identified ER stress associated autophagy as a resistance mechanism to BRAF inhibitors.   Working with collaborators in Chemistry, his lab has designed, synthesized and characterized a novel autophagy inhibitor Lys05, which is more potent than HCQ in animal models. Dr. Amaravadi is also a recognized melanoma medical oncologist and phase I trialist who has served as the site PI or co-investigator on melanoma clinical trials involving BRAF inhibitors, and first in human phase I clinical trials of novel cancer agents. In 2013 he was appointed co- Leader of the Cancer Therapeutics Program of the Abramson Cancer Center. In 2015 he was inducted into the American Society of Clinical Investigation. In 2021 he became co-Director of the Wistar/UPenn Skin SPORE. In 2023 he became Associate Director of Translational Medicine at the Abramson Cancer Center. In 2023 he was inducted into the Association of American Physicians.

Mary Ann Crissey
Lab manager
 mascris@pennmedicine.upenn.edu

Mary Ann S. Crissey has been a Research Specialist and lab manager at the University of Pennsylvania for more than twenty years and has expertise in molecular biology and transgenic mouse techniques, resulting in authorship on seventeen publications. After obtaining a BS in Biology at Pennsylvania State University, she worked at Temple University for ten years including five years researching DNA deletion mechanisms in prokaryotic systems. At Penn, Mary Ann first joined the lab of Dr. Rebecca Taub studying liver regeneration using transgenic mouse models.  She designed and created a knockout mouse utilized in several publications.  Switching gears she went with Dr. Taub to the central nervous system division of a pharmaceutical company for two years, determining which regions of the brain were activated by lead compounds and developing an Alzheimer’s disease transgenic mouse model.  Returning to Penn, Mary Ann joined the intestinal metaplasia group in the gastroenterology division, where she designed two successful transgenic mouse models and was first author on the publications.  Diverse projects included inflammation and precancerous mouse models, immunophenotyping of Barrett’s Esophagus patient samples by flow cytometry, and culture of intestinal organoids for stem cell research. Her research was selected for oral and poster presentation at the international Digestive Disease Week meeting. Since joining the Amaravadi Lab in late 2019, Mary Ann has utilized CRISPR-Cas9 to knock out PPT1 in cell lines and has been developing a conditional PPT1 knockout mouse.

Vaibhav Jain, PhD
Post-doctoral fellow
 vaibhav.jain@pennmedicine.upenn.edu

Dr. Jain graduated from Institute of Genomics and Integrative Biology (IGIB), Delhi, India under the mentorship of Dr. Anurag Agrawal and Dr. Balaram Ghosh, in Respiratory disease biology. He received DBT Junior Research Fellowship (DBT- JRF) award to pursue his research. His thesis work focused on the role of polyamines metabolism in the asthma pathogenesis. In his PhD work, he did a detailed study of polyamine metabolism in vitro and in animal model of asthma and found that the reduction in polyamine catabolism leads to accumulation of polyamines in lung epithelial cells and subsequently to apoptosis. He used a preclinical anti-cancerous compound to solve this metabolic imbalance in animal model of asthma. During his doctoral work he collaboratively worked at Johns Hopkins and Columbia University, USA. He received multiple travel awards to present his work internationally, including prestigious Nature Travel Grants for Gordon Research Conferences as a speaker. Subsequently, he joined Columbia University to work in the field of Pancreatic Cancer using 3D-organoids as a model system. Dr. Jain joined the Amaravadi Lab in 2019 to expand his expertise in the field of metabolism to cancer disease biology. He is actively involved in exploring the metabolic vulnerabilities of autophagy in cancer.

Monika Bhardwaj, PhD
Post-doctoral Fellow
 monika.bhardwaj@pennmedicine.upenn.edu

Dr. Bhardwaj graduated from Daegu University, Daegu, South Korea under the mentorship of Prof. Sun Chul Kang in cancer biology. She was awarded with BRAIN KOREA 21 PLUS (BK21+) and National Research Foundation (NRF) of Korea fellowships from the Korean government to support her research. Her thesis work focused on modulation of autophagy by phytochemicals in colorectal cancer progression. During her doctoral research, she elucidated the role of heat shock transcription factor-1 (HSF-1) as a potential target for treatment outcomes in colorectal cancer. In her detailed study in vitro and in vivo, she found that prevention of transcriptional activation of HSF-1 leads to autophagic cell death in colorectal cancer. She expanded this mechanism of her study in in vitro and in vivo models of drug-resistance. Dr. Bhardwaj translated her PhD work into 3 first-authored research manuscripts and 8 co-authored manuscripts. She has other 2 first-authored research manuscripts on different projects from her graduate lab. She had presented her research work in several international conferences in South Korea. Later, she joined Daegu Institute of Science and Technology (DGIST), Daegu, South Korea to work on development of therapeutic peptides for the treatment of Type-2 diabetes with long-lasting effect. Dr. Bhardwaj was recruited to Amaravadi Lab in April, 2019 to develop her knowledge and skills in autophagy and cancer biology. Her current research work focus on characterization of cell death mechanism by improved autophagy-lysosomal inhibitors in cancer.

Amanda Versace, BS
Research Specialist
 amanda.versace@pennmedicine.upenn.edu

Amanda graduated from Temple University where she studied Biochemistry. In 2011, she was admitted into an undergraduate research program at The Wistar Institute where she gained experience in biomedical research techniques and exposure to cancer studies. In 2017, she joined Thomas Jefferson University as a post baccalaureate researcher and lab manager under Dr. Sara E. Meyer. There she developed mouse models to study specific combinations of epigenetic mutations common in hematological disease. Amanda joined the Amaravadi Lab in 2020 and is learning the field of autophagy and its role in cancer. She is currently working on the chemical biology of novel lysosomal autophagy inhibitors in cancer.

Brandon Peng
Research Specialist
 Brandon.peng@pennmedicine.upenn.edu