Crystal S. Conn, PhD

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Assistant Professor of Radiation Oncology
Affiliation , Penn Pancreatic Cancer Research Center (PCRC)
Affiliation , Penn Institute for RNA Innovation
Department: Radiation Oncology

Contact information
Perelman School of Medicine
3400 Civic Center Blvd., Bldg 421
Smilow Center for Translational Research, Office 8-131
Philadelphia, PA 19104
BS (Major: Biochemistry and Molecular Biology; Minor: Chemistry, Physics)
The Pennsylvania State University, 2007.
PhD (Major: Genetics, Genomics, and Development; Minor: Biochemistry, Genetics)
Cornell University, 2013.
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Description of Research Expertise

Cancer Biology, Adaptive Stress Responses, mRNA Translation, RNA Modifications, Drug targeting, Protein Homeostasis, Ribosome Profiling, Proteomics, in vivo and ex vivo models

Insights into the genetic landscape of patient samples have depicted an explosion of diagnostic and clinical biomarkers using gene expression profiling. However, not all changes at the transcription level translate into proteomic expression, thus limiting the predictive power of mRNA-based prognostics. Genetic alterations also remain difficult to target pharmacologically, and many oncogenes play roles for normal cellular functions which prevents their targeting. Despite these limitations, there arise phenotypic vulnerabilities that malignant cells rely on for their survival.

Dr. Conn's research program is focused on understanding:
1) the signaling pathways that are activated in cancer cells allowing for their dynamic adaptations to stress (nutrient, proteomic, oxidative...etc) during cellular transformation and disease progression
2) how aggressive cancer cells rewire their translational machinery to select distinct mRNAs for protein expression, while 3) identifying unique isoforms created through non-conventional initiation and the functions they serve
4) the relevance of the above processes towards disease detection, improved therapeutical targeting and treatments, with an underlying goal for prevention.

Limited, please contact Dr. Conn to inquire

Selected Publications

Zhang D, Li AM, Hu G, Huang M, Yang F, Zhang L, Wellen KE, Xu X, Conn CS, Zou W, Kahn M, Rhoades SD, Weljie AM, Fuchs SY, Amankulor N, Yoshor D, Ye J, Koumenis C, Gong Y, Fan Y. : PHGDH-mediated endothelial metabolism drives glioblastoma resistance to chimeric antigen receptor T cell immunotherapy. Cell Metabolism 7(35): 517-534, March 2023.

Conn CS*, Yang H*, Tom HJ, Ikeda K, Oses-Prieto JA, Vu H, Oguri Y, Nair S, Gill RM, Kajimura S, DeBerardinis RJ, Burlingame AL, & Ruggero D: The major cap-binding protein eIF4E regulates lipid homeostasis and diet-induced obesity. Nature Metabolism 3: pages244–257, February 2021 Notes: *Denotes co-first.

Tameire F, Verginadis II, Leli NM, Polte C, Conn CS, Ojha R, Salas SC, Chinga F, Monroy AM, Fu W, Wang P, Kossenkov A, Ye J, Amaravadi RK, Ignatova Z, Fuchs SY, Diehl JA, Ruggero D, Koumenis C: ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression. Nat Cell Biol 21(7): 889-899, July 2019.

Wei J, Kishton RJ, Angel M, Conn CS, Dalla-Venezia N, Marcel V, Vincent A, Catez F, Ferré S, Ayadi L, Marchand V, Dersh D, Gibbs JS, Ivanov IP, Fridlyand N, Couté Y, Diaz JJ, Qian SB, Staudt LM, Restifo NP, Yewdell JW: Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance. Molecular cell 73(6): 1162-1173.e5, Mar 2019.

Conn CS*†, Nguyen HG*, Kye Y, Xue L, Forester CM, Cowan JE, Hsieh AC, Cunningham JT, Truillet C, Tameire F, Evans MJ, Evans CP, Yang JC, Hann B, Koumenis C, Walter P, Carroll PR, Ruggero D†: Development of a stress response therapy targeting aggressive prostate cancer. Science Translational Medicine 10(439), May 2018 Notes: *Denotes co-first. †Denotes co-corresponding authors.

Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, Le A, Cowan TM, Ruggero D, Sweet-Cordero EA: Oncogenic KRAS Regulates Amino Acid Homeostasis and Asparagine Biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase. Cancer cell 33(1): 91-107.e6, Jan 2018.

Conn CS, Nguyen HG, Kye Y, Xue L, Hsieh AC, Cunningham JT, Truillet C, Walter P, Carroll PR, and Ruggero D: Sensing stress in cancer: a novel therapy targeting protein synthesis through the unfolded protein response in aggressive prostate cancer. Protein Synthesis and Translational Control, EMBO September 2017 Notes: Oral Presentation.

Truitt ML*, Conn CS*, Shi Z, Pang X, Tokuyasu T, Coady AM, Seo Y, Barna M, Ruggero Davide: Differential Requirements for eIF4E Dose in Normal Development and Cancer. Cell 162(1): 59-71, Jul 2015 Notes: *Denotes equal author contribution.

Zhang X, Gao X, Coots RA, Conn CS, Liu B, and Qian SB: Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18. Nature structural & molecular biology 22(5): 404-10, May 2015.

Conn CS and Qian SB: Nutrient signaling in protein homeostasis: an increase in quantity at the expense of quality. Science signaling 6(271): ra24, Apr 2013.

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Last updated: 06/21/2024
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