Blake Hill, PhD
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.
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.
Structural studies of human fission protein FIS1 reveal a dynamic region important for GTPase DRP1 recruitment and mitochondrial fission.
(Egner JM, Nolden KA, Harwig MC, Bonate RP, De Anda J, Tessmer MH, Noey EL, Ihenacho UK, Liu Z, Peterson FC, Wong GCL, Widlansky ME, Hill RB.) J Biol Chem. 2022 Dec;298(12):102620 PMID: 36272645 PMCID: PMC9747602 SCOPUS ID: 2-s2.0-85143990858 10/23/2022
Novel &lt;i&gt;DNM1L&lt;/i&gt; variants impair mitochondrial dynamics through divergent mechanisms.
(Nolden KA, Egner JM, Collier JJ, Russell OM, Alston CL, Harwig MC, Widlansky ME, Sasorith S, Barbosa IA, Douglas AG, Baptista J, Walker M, Donnelly DE, Morris AA, Tan HJ, Kurian MA, Gorman K, Mordekar S, Deshpande C, Samanta R, McFarland R, Hill RB, Taylor RW, Oláhová M.) Life Sci Alliance. 2022 Aug 01;5(12) PMID: 35914810 PMCID: PMC9354038 SCOPUS ID: 2-s2.0-85135355811 08/02/2022
Histone H3 and H4 tails play an important role in nucleosome phase separation.
(Hammonds EF, Harwig MC, Paintsil EA, Tillison EA, Hill RB, Morrison EA.) Biophys Chem. 2022 Apr;283:106767 PMID: 35158124 PMCID: PMC8963862 SCOPUS ID: 2-s2.0-85124393236 02/15/2022
Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression.
(AbuEid M, McAllister DM, McOlash L, Harwig MC, Cheng G, Drouillard D, Boyle KA, Hardy M, Zielonka J, Johnson BD, Hill RB, Kalyanaraman B, Dwinell MB.) iScience. 2021 Jun 25;24(6):102653 PMID: 34189432 PMCID: PMC8220235 07/01/2021
Mitochondrial Fission Protein 1: Emerging Roles in Organellar Form and Function in Health and Disease.
(Ihenacho UK, Meacham KA, Harwig MC, Widlansky ME, Hill RB.) Front Endocrinol (Lausanne). 2021;12:660095 PMID: 33841340 PMCID: PMC8027123 SCOPUS ID: 2-s2.0-85103798701 04/13/2021
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 SCOPUS ID: 2-s2.0-85086424880 06/13/2020
Mitochondrial regulation of diabetic vascular disease: an emerging opportunity.
(Widlansky ME, Hill RB.) Transl Res. 2018 Dec;202:83-98 PMID: 30144425 PMCID: PMC6218302 SCOPUS ID: 2-s2.0-85052836555 08/26/2018
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 Sep 21;293(38):14891-14904 PMID: 30087121 PMCID: PMC6153299 SCOPUS ID: 2-s2.0-85054023214 08/09/2018
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 Jul 19;71(2):216-228.e7 PMID: 30029002 PMCID: PMC6091221 SCOPUS ID: 2-s2.0-85049861465 07/22/2018
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 Jul 01;552:81-99 PMID: 29505779 PMCID: PMC6322684 SCOPUS ID: 2-s2.0-85048014256 03/06/2018
Development and Validation of 2D Difference Intensity Analysis for Chemical Library Screening by Protein-Detected NMR Spectroscopy.
(Egner JM, Jensen DR, Olp MD, Kennedy NW, Volkman BF, Peterson FC, Smith BC, Hill RB.) Chembiochem. 2018 Mar 02;19(5):448-458 PMID: 29239081 PMCID: PMC5844354 SCOPUS ID: 2-s2.0-85041064927 12/15/2017
Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins.
(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 Mar;38(3):622-635 PMID: 29419407 PMCID: PMC5823793 SCOPUS ID: 2-s2.0-85047900228 02/09/2018