个人简介

“... like most other CR authors, was born and majored in chemistry. On a sunny day in May of 1980, her favorite professor at UVa, Tom Cromartie, suggested that she go to Brandeis and get a Ph.D. with Bob Abeles. She went on to do postdoctoral work at UCSF, first with C.C. Wang studying protozoan parasites, and later with Bill Rutter, where she converted trypsin into chymotrypsin. Now almost thirty years after that pivotal May day, she is back at Brandeis... Chemical Reviews 2009

研究领域

Relationship between protein structure and function in enzyme catalysis and inhibitor action. Understanding the effects of mutations in vivo.

My laboratory uses approaches derived from both chemistry and biology to investigate molecular mechanisms of cellular biochemistry and physiology. Projects are organized around the themes of purine/pyrimidine metabolism and protease action and include problems in inhibitor design, protein engineering and cellular metabolism. Most projects have clinical relevance. Techniques vary with the particular project, and can entail molecular biology, single molecule experiments, organic synthesis, protein crystallography and NMR spectroscopy as well as protein purification, enzyme kinetics and mutagenesis.

近期论文

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Lawson, Ann P.; Bak, Daniel W.; Shannon, D. Alexander; Long, Marcus J.C.; Vijaykumar, Tushara; Yu, Runhan; El Oualid, Farid; Weerapana, Eranthie. and Hedstrom, Lizbeth. "Identification of Deubiquitinase Targets of Isothiocyanates using SILAC-Assisted Quantitative Mass Spectrometry." Oncotarget in press. (2017). (forthcoming) Hedstrom, Lizbeth. "The Bare Essentials of Antibiotic Target Validation." ACS Infect Dis. 3. (2017): 2-4. Shi, Yuntao; Long, Marcus J.C.; Rosenberg, Masha M.; Li, Shican; Kobjack, Aimee; Lessans, Philip; Coffey, Rory T. and Hedstrom, Lizbeth. "Boc3Arg-linked ligands induce degradation by localizing target proteins to the 20S proteasome.." ACS Chemical Biology 11. (2017): 3328-3337. Zhang, Susan; Burns-Huang, Kristin E.; Janssen, Guido V.; Li, Huilin; Weber-Ban, Eilika; Ovaa, Huib; Hedstrom, Lizbeth and Darwin,, K. Heran. "Mycobacterium tuberculosis proteasome accessory factor A (PafA) can transfer prokaryotic ubiquitin-like protein (Pup) between substrates." mBio 8. (2017): e00122-17. Coffey, Rory T.; Shi, Yuntao; Long, Marcus J.C.; Marr II, Michael T. and Hedstrom, Lizbeth. "Ubiquilin Mediated Small Molecule Inhibition of Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling." J. Biol. Chem. 291. (2016): 5221-33. Hedstrom, Lizbeth. "Cryptosporidium: a first step toward tractability.." Trends in Parasitology 31. (2016): 401-2. Lawson, Ann P.; Long, Marcus J. C.; Coffey,Rory T.; Qian,Yu; Weerapana, Eranthie; El Oualid, Farid and Hedstrom, Lizbeth.. "Naturally Occurring Isothiocyanates Inhibit Deubiquitinating Enzymes." Cancer Research 75. (2016): 5130-5142. Makowska-Grzyska, Magdalena; Kim, Youngchang; Gorla, Suresh Kumar; Wei, Yang; Mandapati, Kavitha; Zhang, Minjia; Maltseva, Natalia; Modi, Gyan; Boshoff, Helena I.; Gu, Minyi; Aldrich, Courtney; Cuny, Gregory D.; Hedstrom, Lizbeth and Joachimiak, And. "Mycobacterium tuberculosis IMPDH in complexes with substrates, products and antitubercular compounds.." PLoS ONE 10. (2016): e0138976. Rosenberg, Masha M.; Redfield, Alfred G.; Roberts, Mary F. and Lizbeth Hedstrom. "Substrate and Cofactor Dynamics on Guanosine Monophosphate Reductase Probed by High Resolution Field Cycling 31P NMR Relaxometry." J. Biological Chemistry 291. (2016): 22988-22998. Wei, Yang; Kuzmič, Petr; Yu, Runhan; Modi, Gyan and Hedstrom, Lizbeth. "Inhibition of IMPDH from Bacillus anthracis: Mechanism revealed by pre-steady state kinetics." Biochemistry 55. (2016): 5279-88. Kim, Youngchang; Makowska-Grzyska, Magdalena; Gorla, Suresh Kumar; Gollapalli, Deviprasad R.; Cuny, Gregory D.; Joachimiak, Andrzej and Hedstrom, Lizbeth. "Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity." Acta Cryst. Sec. F (2015). Makowska-Grzyska M, Kim Y, Maltseva N, Osipiuk J, Gu M, Zhang M, Mandapati K, Gollapalli DR, Gorla SK, Hedstrom L, Joachimiak A.. "A Novel Cofactor-binding Mode in Bacterial IMP Dehydrogenases Explains Inhibitor Selectivity.." J Biol Chem. 290. (2015): 5893-911. Gorla, Suresh Kumar; McNair, Nina N.; Yang, Guangyi; Gao, Song; Hu, Ming; Jala, Venkatakrishna R.; Haribabu, Bodduluri; Striepen, Boris; Cuny, Gregory D.; Mead, Jan R. and Hedstrom, Lizbeth. "Validation of IMP dehydrogenase inhibitors in a mouse model of cryptosporidiosis." Antimicrob. Agents Chemother. 58. (2014): 1603-14. Kuang, Yi; Long, Marcus J. C.; Zhou, Ji; Shi, Junfen; Gao, Yuan; Xu, Chen; Hedstrom, Lizbeth and Xu, Bing.. "Prion-like Nanofibrils of Small Molecules (PriSM) Selectively Inhibit Cancer Cells by Frustrating Cytoskeleton Dynamics.." J. Biol. Chem. 289. (2014): 29208-18. Mandapati, Kavitha; Gorla, Suresh Kumar; House, Amanda L.; McKenney, Elizabeth S.; Zhang, Minjia; Rao, Suraj Nagendra*; Gollapalli, Deviprasad R.; Mann, Barbara J.; Goldberg, Joanna B.; Cuny, Gregory D.; Glomski, Ian J. and Hedstrom, Lizbeth.. "Repurposing Cryptosporidium Inosine 5’-monophosphate Dehydrogenase Inhibitors as Potential Antibacterial Agents.." ACS Med. Chem. Lett, 5. (2014): 846-850. Sun, Zhuming; Khan, Jihan; Makowska-Grzyska, Magdalena; Zhang, Minjia; Cho, Joon Hyun; Suebsuwong, Chalada; Vo, Pascal; Gollapalli, Deviprasad R.; Kim, Youngchang; Joachimiak, Andrzej; Hedstrom, Lizbeth and Gregory D. Cuny. "Synthesis, in vitro evaluation and co-crystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum inosine 5′-monophosphate dehydrogenase (CpIMPDH) inhibitors." J. Med. Chem. 57. (2014): 10544-50.. Gao, Yua, Long, Marcus J.C; Shi, Junfeng; Hedstrom, Lizbeth and Xu, Bing. "Using supramolecular hydrogel to discover the interactions between proteins and molecular nanofibers of small molecules." Chem. Commun. (Camb) 48. (2013): 8404-6. Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; *Chin, James En Wai; Liu, Xiaoping; Striepen, Boris; Makowska-Grzyska, Magdalena; Kim, Youngchang; Joachimiak, Andrzej; Hedstrom, Lizbeth and Cuny, Gregory D.. "Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase.." J. Med. Chem. 56. (2013): 4028-43. Hedstrom, Lizbeth. "IMP dehydrogenase: the dynamics of reaction specificity." Proceedings of the 5th International Beilstein Symposium on Experimental Standard Conditions of Enzyme Characterizations (ESCEC)., 2013 Johnson, Corey R.; Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Liu, Xiaoping; Striepen, Boris; Mead, Jan R.; Cuny, Gregory D. and Hedstrom, Lizbeth. "Phthalazinone Inhibitors of Inosine-5’-Monophosphate Dehydrogenase from Cryptosporidium parvum." Biorg. Med. Chem. Lett. 23. (2013): 1004-7. Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Liu, Xiaoping; Sharling, Lisa; Gollapalli, Deviprasad R; Striepen, Boris; Hedstrom, Lizbeth and Cuny, Gregory D.. "Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase." J. Med. Chem. 55. 7759-71 (2012). Hansen, B. G., Sun, X. E., Genee, H. J., Kaas, C. S., Nielsen, J. B., Mortensen, U. H., Frisvad, J. C., Hedstrom, L.. "Adaptive evolution of drug targets in producer and non-producer organisms." Biochemical Journal 441. (2012): 219-226. Hedstrom, Lizbeth. "The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)8 barrel enzymes." Critical Reviews In Biochemistry & Molecular Biology 47. (2012): 250-63. Kirubakaran, S., Gorla, S. K., Sharling, L., Zhang, M. J., Liu, X. P., Ray, S. S., MacPherson, I. S., Striepen, B., Hedstrom, L., Cuny, G. D.. "Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH." Bioorganic & Medicinal Chemistry Letters 22. 5 (2012): 1985-1988. Long, Marcus J. C. and Hedstrom, Lizbeth. "Mushroom Tyrosinase Oxidizes Tyrosine-rich Sequences, Allowing Selective Protein Functionalization." ChemBiochem 13. (2012): 1818-25.