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Donita C. Brady, Ph.D.
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Harrison McCrea Dickson, M.D. and Clifford C. Baker, M.D. Presidential Professor
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Abramson Family Cancer Research Institute, University of Pennsylvania
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Abramson Cancer Center Tumor Biology Program, University of Pennsylvania
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Department: Cancer Biology
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Graduate Group Affiliations
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Contact information
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421 Curie Blvd.
36 Room 612 BRB II/III
Philadelphia, PA 19104
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36 Room 612 BRB II/III
Philadelphia, PA 19104
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Office: 215-573-9705
32 Fax: 215-573-6725
32 Lab: 215-573-9706
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32 Fax: 215-573-6725
32 Lab: 215-573-9706
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Publications
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Links
b5 Search PubMed for articles
7c Department of Cancer Biology Faculty Page
6a The Department of Cancer Biology
6e Abramson Family Cancer Research Institute
5f Brady Lab Website
5d Brady Lab Twitter
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b5 Search PubMed for articles
7c Department of Cancer Biology Faculty Page
6a The Department of Cancer Biology
6e Abramson Family Cancer Research Institute
5f Brady Lab Website
5d Brady Lab Twitter
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Education:
21 9 B.S. 16 (Chemistry) c
38 Radford University, Radford, VA, 2003.
21 a Ph.D. 19 (Pharmacology) c
44 University of North Carolina at Chapel Hill, 2008.
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Permanent link21 9 B.S. 16 (Chemistry) c
38 Radford University, Radford, VA, 2003.
21 a Ph.D. 19 (Pharmacology) c
44 University of North Carolina at Chapel Hill, 2008.
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88 The research interests of our laboratory lie at the intersection of cancer biology, signal transduction, and metal homeostasis.
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19 Keywords:
9a Cancer Biology, Metal Homeostasis, Signal Transduction, Kinases, Small GTPases, Pharmacologic Interventions, Genetically Engineered Mouse Models
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21 Research Details:
126 The Brady Lab is part of the Department of Cancer Biology and the Abramson Family Cancer Research Institute in the Perelman School of Medicine at the University of Pennsylvania. Our research program at Penn explores two key areas in cancer biology to understand what fuels cancer cells.
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40 Mapping and Leveraging Metal Signaling in Cancer
4ed We’re looking beyond the usual nutrients—proteins, fats, and sugars—to examine the contribution of metals to cancer growth. Metals are essential for many cellular processes, supporting the structure and function of DNA, RNA, and a large number of proteins. Our bodies rely on dietary metals, specific transporters to absorb them, and tight regulation to keep metal levels balanced. However, much remains unknown about how metals from our diet fine-tune biological functions or how cells adjust to changes in metal availability. Our research team is investigating these questions by studying how cells maintain metal balance and respond to metal fluctuations, focusing on how metal-protein interactions drive cellular processes by intersecting with cellular metabolic pathways. We’re also exploring whether metal needs shift as stem cells, which drive tissue growth and repair, mature into specialized types or are activated from a resting state to start repairs in a process that can go wrong and may be one of the first steps toward cancer development. This work could lead to new insights into how metals support tissue health and development, potentially uncovering new ways to treat diseases like cancer where these processes are disrupted.
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4f Unlocking the Chemical Space of Cancer-Associated Perturbations
36f Although detection of genetic differences between cancer and normal cells has led to advances in precision medicine, only a small fraction of patients benefit from these approaches. We’re expanding beyond genetics to focus on proteins, which directly drive cancer initiation, growth, and spread. By tracking changes in protein function, we can better predict treatment responses, identify new cancer vulnerabilities, and develop targeted therapies. To advance this, we created the Probe Enabled Activity Reporting (PEAR) platform with colleagues from biochemistry, cancer biology, and radiology. PEAR uses a unique probe to capture the full range of proteins in cancer cells, identifying potential drug targets that genetic analysis might miss. This approach could significantly enhance precision oncology and drug discovery, opening doors for better cancer treatments.
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1c Lab Members:
22 Graduate Students:
15 Ahlenne Abreu
14 Yuxuan Chang
14 Islam Elsaid
15 Nate McKnight
25 Postdoctoral Fellows:
1c Santanu Ghosh, Ph.D.
1e Ralph White III, Ph.D.
24 Research Technician:
15 Andrew Jarvis
2b Administrative Coordinator:
13 Deb Sneddon
1a dsneddon@upenn.edu
14 215-573-2281
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22 Rotation Projects:
71 Rotation projects are available in each area of interest in the lab. Please contact Dr. Brady for details.
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Description of Research Expertise
2c Research Interests:88 The research interests of our laboratory lie at the intersection of cancer biology, signal transduction, and metal homeostasis.
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19 Keywords:
9a Cancer Biology, Metal Homeostasis, Signal Transduction, Kinases, Small GTPases, Pharmacologic Interventions, Genetically Engineered Mouse Models
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21 Research Details:
126 The Brady Lab is part of the Department of Cancer Biology and the Abramson Family Cancer Research Institute in the Perelman School of Medicine at the University of Pennsylvania. Our research program at Penn explores two key areas in cancer biology to understand what fuels cancer cells.
8
40 Mapping and Leveraging Metal Signaling in Cancer
4ed We’re looking beyond the usual nutrients—proteins, fats, and sugars—to examine the contribution of metals to cancer growth. Metals are essential for many cellular processes, supporting the structure and function of DNA, RNA, and a large number of proteins. Our bodies rely on dietary metals, specific transporters to absorb them, and tight regulation to keep metal levels balanced. However, much remains unknown about how metals from our diet fine-tune biological functions or how cells adjust to changes in metal availability. Our research team is investigating these questions by studying how cells maintain metal balance and respond to metal fluctuations, focusing on how metal-protein interactions drive cellular processes by intersecting with cellular metabolic pathways. We’re also exploring whether metal needs shift as stem cells, which drive tissue growth and repair, mature into specialized types or are activated from a resting state to start repairs in a process that can go wrong and may be one of the first steps toward cancer development. This work could lead to new insights into how metals support tissue health and development, potentially uncovering new ways to treat diseases like cancer where these processes are disrupted.
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4f Unlocking the Chemical Space of Cancer-Associated Perturbations
36f Although detection of genetic differences between cancer and normal cells has led to advances in precision medicine, only a small fraction of patients benefit from these approaches. We’re expanding beyond genetics to focus on proteins, which directly drive cancer initiation, growth, and spread. By tracking changes in protein function, we can better predict treatment responses, identify new cancer vulnerabilities, and develop targeted therapies. To advance this, we created the Probe Enabled Activity Reporting (PEAR) platform with colleagues from biochemistry, cancer biology, and radiology. PEAR uses a unique probe to capture the full range of proteins in cancer cells, identifying potential drug targets that genetic analysis might miss. This approach could significantly enhance precision oncology and drug discovery, opening doors for better cancer treatments.
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1c Lab Members:
22 Graduate Students:
15 Ahlenne Abreu
14 Yuxuan Chang
14 Islam Elsaid
15 Nate McKnight
25 Postdoctoral Fellows:
1c Santanu Ghosh, Ph.D.
1e Ralph White III, Ph.D.
24 Research Technician:
15 Andrew Jarvis
2b Administrative Coordinator:
13 Deb Sneddon
1a dsneddon@upenn.edu
14 215-573-2281
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22 Rotation Projects:
71 Rotation projects are available in each area of interest in the lab. Please contact Dr. Brady for details.
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1c9 Grasso, M., Bond, G.J.*, Kim, Y.J.*, Boyd, S., Dzebo, M.M., Valenzuela, S., Tsang, T., Schibrowsky, N.A., Alwan, K.B., Blackburn, N.J., Burslem, G.M., Wittung-Stafshede, P., Winkler, D.D., Marmorstein, R., & Brady, D.C. : The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation. J Biol Chem 297(6), December 2021 Notes: (* shared second authorship)
121 Davis, C.I., Gu, X., Kiefer, R. M., Ralle, M., Gade, T.P., & Brady D.C.: Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation. Metallomics 12(12): 1995-008, December 2020.
f3 Blockhuys, S., Brady D.C., & Wittung-Stafshede, P.: Evaluation of copper chaperone ATOX1 as prognostic biomarker in breast cancer. Breast Cancer 27(3): 505-509, May 2020.
14a Tsang, T.*, Posimo, J.M.*, Guidiel, A.A., Cicchini, M., Feldser, D.M., & Brady D.C.: Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat Cell Biol 22(4): 412-424, April 2020 Notes: (* shared first authorship).
11e Kim, Y.J., Tsang, T., Posimo, J.M, Anderson, G.R., & Brady, D.C.: Inhibition of BCL2 family members increases the efficacy of copper chelation in BRAFV600E-driven melanoma. Cancer Res 80(7): 1387-1400 April 2020.
122 Kim, Y.J., Bond, G.J., Tsang, T., Posimo, J.M, Busino, L., & Brady, D.C.: Copper chaperone ATOX1 is required for MAPK signaling and growth in BRAF mutation-positive melanoma. Metallomics 11(8): 1430-1440 August 2019
20f Rasool, R.U.*, Natesan, R.*, Deng, Q.*, Aras, S., Lal, P., Effron, S.S., Mitchell-Velasquez, E., Posimo, J.M., Carskadon, S., Baca, S.C., Pomerantz, M.M., Siddiqui, J., Schwartz, L.E., Lee, D.J., Palanisamy, N., Narla, G., Den, R.B., Freedman, M.L., Brady, D.C., & Asangani, I.A.: CDK7 Inhibition Suppresses Castration-Resistant Prostate Cancer through MED1 Inactivation. Cancer Discov 9(11): 1538-1555, November 2019 Notes: (* shared first authorship).
1b9 Chung, C.Y.*, Posimo, J.M.*, Lee, S.*, Tsang, T.*, Davis, J.M., Brady, D.C.#, & Chang, C.J.#: Activity-based ratiometric FRET probe reveals oncogene-driven changes in labile copper pools induced by altered glutathione metabolism Proc. Natl. Acad. Sci. U. S. A. 116(37): 18285-18294, September 2019 Notes: (* shared first authorship or # shared corresponding author).
1c2 Katona, B.W., Glynn, R.A., Paulosky, K.E., Feng, Z., Davis, C.I., Ma, J., Berry, C.T., Szigety, K.M., Matkar, S., Liu, Y., Wang, H., Wu, Y., He, X., Freedman, B.D., Brady, D.C., & Hua, X: Combined menin and EGFR inhibitors synergize to suppress colorectal cancer via EGFR-independent and calcium-mediated repression of SKP2 transcription. Cancer Res 79(9): 2195-2207 May 2019.
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Selected Publications
133 Roby, K.C., Lieberman, A., Kim, B., Rodriguez, N., Posimo, J.M., Tsang, T., Vergindas, I.I., Pure, E., Brady, D.C., Koumenis, C., & Ryeom, S.W. : Loss of p19Arf Promotes Fibroblast Survival During Leucine Deprivation. Biol Open 2022.1c9 Grasso, M., Bond, G.J.*, Kim, Y.J.*, Boyd, S., Dzebo, M.M., Valenzuela, S., Tsang, T., Schibrowsky, N.A., Alwan, K.B., Blackburn, N.J., Burslem, G.M., Wittung-Stafshede, P., Winkler, D.D., Marmorstein, R., & Brady, D.C. : The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation. J Biol Chem 297(6), December 2021 Notes: (* shared second authorship)
121 Davis, C.I., Gu, X., Kiefer, R. M., Ralle, M., Gade, T.P., & Brady D.C.: Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation. Metallomics 12(12): 1995-008, December 2020.
f3 Blockhuys, S., Brady D.C., & Wittung-Stafshede, P.: Evaluation of copper chaperone ATOX1 as prognostic biomarker in breast cancer. Breast Cancer 27(3): 505-509, May 2020.
14a Tsang, T.*, Posimo, J.M.*, Guidiel, A.A., Cicchini, M., Feldser, D.M., & Brady D.C.: Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat Cell Biol 22(4): 412-424, April 2020 Notes: (* shared first authorship).
11e Kim, Y.J., Tsang, T., Posimo, J.M, Anderson, G.R., & Brady, D.C.: Inhibition of BCL2 family members increases the efficacy of copper chelation in BRAFV600E-driven melanoma. Cancer Res 80(7): 1387-1400 April 2020.
122 Kim, Y.J., Bond, G.J., Tsang, T., Posimo, J.M, Busino, L., & Brady, D.C.: Copper chaperone ATOX1 is required for MAPK signaling and growth in BRAF mutation-positive melanoma. Metallomics 11(8): 1430-1440 August 2019
20f Rasool, R.U.*, Natesan, R.*, Deng, Q.*, Aras, S., Lal, P., Effron, S.S., Mitchell-Velasquez, E., Posimo, J.M., Carskadon, S., Baca, S.C., Pomerantz, M.M., Siddiqui, J., Schwartz, L.E., Lee, D.J., Palanisamy, N., Narla, G., Den, R.B., Freedman, M.L., Brady, D.C., & Asangani, I.A.: CDK7 Inhibition Suppresses Castration-Resistant Prostate Cancer through MED1 Inactivation. Cancer Discov 9(11): 1538-1555, November 2019 Notes: (* shared first authorship).
1b9 Chung, C.Y.*, Posimo, J.M.*, Lee, S.*, Tsang, T.*, Davis, J.M., Brady, D.C.#, & Chang, C.J.#: Activity-based ratiometric FRET probe reveals oncogene-driven changes in labile copper pools induced by altered glutathione metabolism Proc. Natl. Acad. Sci. U. S. A. 116(37): 18285-18294, September 2019 Notes: (* shared first authorship or # shared corresponding author).
1c2 Katona, B.W., Glynn, R.A., Paulosky, K.E., Feng, Z., Davis, C.I., Ma, J., Berry, C.T., Szigety, K.M., Matkar, S., Liu, Y., Wang, H., Wu, Y., He, X., Freedman, B.D., Brady, D.C., & Hua, X: Combined menin and EGFR inhibitors synergize to suppress colorectal cancer via EGFR-independent and calcium-mediated repression of SKP2 transcription. Cancer Res 79(9): 2195-2207 May 2019.
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