
Blake Hill, PhD
Professor
Locations
- Biochemistry
TBRC C2970
Contact Information
Education
Biography
Dr. Hill earned a PhD from Yale University (Biophysical Chemistry) in 1995 where he was a Frederick W. and Elsie L. Heyl graduate fellow. His postdoctoral training in protein design and engineering was completed at the University of Pennsylvania School of Medicine where he was awarded NIH and George W. Raiziss fellowships. Previously, he earned a bachelor's degree from Kalamazoo College followed by a stint at a major pharmaceutical company where he developed in vitro and in vivo models for oral bioavailability of peptide drugs. In 2000, Dr. Hill joined the faculty at Johns Hopkins University where began his NIH-funded research program in the molecular basis of mitochondrial homeostasis. He joined the faculty of the Medical College of Wisconsin in 2012 to pursue translational applications of his laboratory's basic research on the mechanism of mitochondrial homeostasis.
Research Experience
- Biochemistry
Research Interests
Defects in mitochondrial fission and fusion cause or contribute to human diseases including cancer, neuropathies, cardiomyopathies, and even death. Our goal is to understand molecular basis of these defects in order to identify new therapeutic routes for these diseases.
We determine how proteins interact with other biological macromolecules to control these basic membrane fission and fusion processes in healthy, diseased, and dying cells. We strive to understand these interactions on a physicochemical level, with an eye for gleaning universal principles of protein chemistry including interactions with membrane bilayers that are fundamental to a wide variety of cellular processes.
A key feature of some proteins that affect mitochondrial homeostasis is the structural transformation from soluble to membrane-bound conformations, a phenomenon referred to as amphitropism. Associating with, or dissociating from, a membrane (i.e. amphitropism) has significant functional consequences for numerous biological processes: it can affect enzymatic activity (CCT, PLC), can promote changes in organelle and cell morphology (MinD, dynamins), or can act as a regulatory switch in various signaling cascades (PKC, ESCRTs). However, neither what drives proteins to reversibly interact with membranes nor how this function controls biological outcomes are clearly understood. These interactions are likely governed by evolutionarily conserved mechanisms that are still being determined and is one focus of our efforts.
Towards these goals, we use a wide range of tools including genetic, cell biological, biochemical, and biophysical methods including NMR spectroscopy and x-ray crystallography for protein structure determination. Please visit the Hill Lab website for more information.
Publications
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Isolation and Analysis of Mitochondrial Fission Enzyme DNM1 from Saccharomyces cerevisiae.
(Kennedy NW, Picton LK, Hill RB.) Methods Mol Biol. 2020;2159:3-15 PMID: 32529359 PMCID: PMC8040746 06/13/2020
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Mitochondrial regulation of diabetic vascular disease: an emerging opportunity.
(Widlansky ME, Hill RB.) Transl Res. 2018 12;202:83-98 PMID: 30144425 PMCID: PMC6218302 SCOPUS ID: 2-s2.0-85052836555 08/26/2018
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Mitochondria-targeted drugs stimulate mitophagy and abrogate colon cancer cell proliferation.
(Boyle KA, Van Wickle J, Hill RB, Marchese A, Kalyanaraman B, Dwinell MB.) J Biol Chem. 2018 09 21;293(38):14891-14904 PMID: 30087121 PMCID: PMC6153299 SCOPUS ID: 2-s2.0-85054023214 08/09/2018
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SRCP1 Conveys Resistance to Polyglutamine Aggregation.
(Santarriaga S, Haver HN, Kanack AJ, Fikejs AS, Sison SL, Egner JM, Bostrom JR, Seminary ER, Hill RB, Link BA, Ebert AD, Scaglione KM.) Mol Cell. 2018 07 19;71(2):216-228.e7 PMID: 30029002 PMCID: PMC6091221 SCOPUS ID: 2-s2.0-85049861465 07/22/2018
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Methods for imaging mammalian mitochondrial morphology: A prospective on MitoGraph.
(Harwig MC, Viana MP, Egner JM, Harwig JJ, Widlansky ME, Rafelski SM, Hill RB.) Anal Biochem. 2018 07 01;552:81-99 PMID: 29505779 PMCID: PMC6322684 SCOPUS ID: 2-s2.0-85048014256 03/06/2018
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(Egner JM, Jensen DR, Olp MD, Kennedy NW, Volkman BF, Peterson FC, Smith BC, Hill RB.) Chembiochem. 2018 03 02;19(5):448-458 PMID: 29239081 PMCID: PMC5844354 SCOPUS ID: 2-s2.0-85041064927 12/15/2017
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(Ma C, Beyer AM, Durand M, Clough AV, Zhu D, Norwood Toro L, Terashvili M, Ebben JD, Hill RB, Audi SH, Medhora M, Jacobs ER.) Arterioscler Thromb Vasc Biol. 2018 03;38(3):622-635 PMID: 29419407 PMCID: PMC5823793 SCOPUS ID: 2-s2.0-85047900228 02/09/2018
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Molecular Motor Dnm1 Synergistically Induces Membrane Curvature To Facilitate Mitochondrial Fission.
(Lee MW, Lee EY, Lai GH, Kennedy NW, Posey AE, Xian W, Ferguson AL, Hill RB, Wong GCL.) ACS Cent Sci. 2017 Nov 22;3(11):1156-1167 PMID: 29202017 PMCID: PMC5704292 12/05/2017
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Removal of a consensus proline is not sufficient to allow tetratricopeptide repeat oligomerization.
(Bakkum AL, Hill RB.) Protein Sci. 2017 Oct;26(10):1974-1983 PMID: 28707340 PMCID: PMC5606541 07/15/2017
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(Bordt EA, Clerc P, Roelofs BA, Saladino AJ, Tretter L, Adam-Vizi V, Cherok E, Khalil A, Yadava N, Ge SX, Francis TC, Kennedy NW, Picton LK, Kumar T, Uppuluri S, Miller AM, Itoh K, Karbowski M, Sesaki H, Hill RB, Polster BM.) Dev Cell. 2017 03 27;40(6):583-594.e6 PMID: 28350990 PMCID: PMC5398851 03/30/2017
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(Cahill TJ, Leo V, Kelly M, Stockenhuber A, Kennedy NW, Bao L, Cereghetti GM, Harper AR, Czibik G, Liao C, Bellahcene M, Steeples V, Ghaffari S, Yavari A, Mayer A, Poulton J, Ferguson DJ, Scorrano L, Hettiarachchi NT, Peers C, Boyle J, Hill RB, Simmons A, Watkins H, Dear TN, Ashrafian H.) J Biol Chem. 2016 12 02;291(49):25762 PMID: 27913663 PMCID: PMC5207272 12/04/2016
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(Koppenol-Raab M, Harwig MC, Posey AE, Egner JM, MacKenzie KR, Hill RB.) J Biol Chem. 2016 09 23;291(39):20329-44 PMID: 27496949 PMCID: PMC5034033 08/09/2016