Mills, Edward M., Ph.D.
Assistant Professor
PHR 5.218E
512-471-6699
ted_mills@mail.utexas.edu

KATSUYA HIRASAKA, PhD
Visiting Scholar
Assistant Professor, University of Tokushima, Tokushima, Japan
Email: hirasaka@mail.utexas.edu

My research interests are focused on skeletal muscle metabolism and pathophysiology.  In my former lab in Tokushima, Japan, I identified reactive oxidant species and the E3 ubiquitin ligase Cbl-b as critical components of the proteolytic cascade that leads to muscle degeneration in response to lack of use or microgravity.  In the Mills lab, my project explores how intracellular redox signals coordinate skeletal muscle fatty acid metabolism, insulin sensitivity, and mitochondrial thermogenesis regulated by uncoupling protein 3 (UCP3).   

Education:
B.S. Fisheries Science, Nagasaki University, Nakagaski, Japan
M.S. Nutrition, University of Tokushima, Tokushima, Japan
Ph.D. Nutrition, University of Tokushima, Tokushima, Japan

Publications:
Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T (2009) Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading Mol Cell Biol 29: 4798-4811

Mikura M, Yamaoka I, Doi M, Kawano Y, Nakayama M, Nakao R, Hirasaka K, Okumura Y, Nikawa T (2009) Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats Anesthesiology 110: 81-88

Hirasaka K, Kohno S, Goto J, Furochi H, Mawatari K, Harada N, Hosaka T, Nakaya Y, Ishidoh K, Obata T, Ebina Y, Gu H, Takeda S, Kishi K, Nikawa T (2007) Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice Diabetes 56: 2511-2522

Suzue N, Nikawa T, Onishi Y, Yamada C, Hirasaka K, Ogawa T, Furochi H, Kosaka H, Ishidoh K, Gu H, Takeda S, Ishimaru N, Hayashi Y, Yamamoto H, Kishi K, Yasui N (2006) Ubiquitin ligase Cbl-b downregulates bone formation through suppression of IGF-I signaling in osteoblasts during denervation J Bone Miner Res 21: 722-734

Hirasaka K, Nikawa T, Yuge L, Ishihara I, Higashibata A, Ishioka N, Okubo A, Miyashita T, Suzue N, Ogawa T, Oarada M, Kishi K (2005) Clinorotation prevents differentiation of rat myoblastic L6 cells in association with reduced NF-kappa B signaling Biochim Biophys Acta 1743: 130-140

Nikawa T, Ishidoh K, Hirasaka K, Ishihara I, Ikemoto M, Kano M, Kominami E, Nonaka I, Ogawa T, Adams GR, Baldwin Km, Yasui N, Kishi K, Takeda S (2004) Skeletal muscle gene expression in space-flown rats FASEB J 18: 522-524

ELLEN ABRAMSON
Graduate Student – PhD Candidate
Institute for Cellular and Molecular Biology
Email: eabramson@mail.utexas.edu

Emerging evidence implicates reactive oxygen species (ROS) as important mediators of signal transduction cascades involved in determination of cell fates ranging from apoptosis to differentiation.  One barrier towards understanding the functional roles of oxidants is the identification of specific protein targets of oxidation in vivo.  My project deals with the orphan nuclear receptor NGFI-B, a steroid/thyroid hormone superfamily transcription factor critical for skeletal muscle development and physiology, and a regulator of apoptosis in cancer cells.   I recently discovered that NGFI-B also regulates mitochondrial membrane potential in a manner apparently independent from its roles as a transcription factor. 

Education:
B.S. Biology, Trinity University, San Antonio, TX

Publications:
Kenaston MA, Abramson E, Pfeiffer ME, Mills EM (2009) Chapter 70: Toxicology of Skeletal Muscle General and Applied Toxicology 3rd Ed. Wiley, ISBN#978-470-72327-2

Mills EM, Weaver KL, Abramson E, Pfeiffer M, Sprague JE (2008) Influence of dietary fats on ecstasy-induced hyperthermia Brit J Pharmacol 151: 1103-1108

ALEXANDER KENASTON
Graduate Student – PhD Candidate
College of Pharmacy
Email: alex.kenaston@mail.utexas.edu

Uncoupling proteins (UCPs) are mitochondrial transmembrane proteins that waste energy in the form of heat.  Uncoupling protein 3 is enriched in skeletal muscle, an established thermogenic organ. UCP3 knockout (KO) mice almost completely lack the hyperthermic responses to the widely-abused drugs ecstasy and methamphetamine.  My project uses multiple mouse strains and cultured primary and secondary myocytes cell lines to determine the physiological and cellular mechanisms of UCP3-driven thermogenesis.   

Education:
B.S. Nursing, University of Texas at Austin, Austin, TX

Publications:
Kenaston MA, Abramson E, Pfeiffer ME, Mills EM (2009) Chapter 70: Toxicology of Skeletal Muscle General and Applied Toxicology 3rd Ed. Wiley, ISBN#978-470-72327-2

Banks ML, Buzard SK, Gehret CM, Monroy AN, Kenaston MA, Mills EM, Sprague JE (2009) Pharmacodynamic characterization of insulin on MDMA-induced thermogenesis Eur J Pharmacol 615: 257-261

Wyeth RP, Mills EM, Ullman A, Kenaston MA, Burwell J, Sprague JE (2009) The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is sensitive to sex differences Toxicol Appl Pharmacol 235: 33-38

MATT PFEIFFER
Graduate Student – PhD Candidate
College of Pharmacy
Email: avatarloki@mail.utexas.edu

Uncoupling proteins are highly conserved members of the mitochondrial anion superfamily.  Unlike other UCP homologues, only UCP4 is present in the nematode Caenorhabditis elegans (C. elegans), suggesting that it is the ancestral uncoupling protein from which other homologues diverged.  UCP4 knockout worms are obese, accumulate triglycerides, and have deficiencies in the import of mitochondrial substrates.  My project involves molecular, cellular, and biochemical approaches to characterize the physiologic functions of UCP4 and the mechanisms by which UCP4 regulates mitochondrial functions. 

Education:
B.S. Microbiology, University of Texas at Austin, Austin, TX

Publications:
Kenaston MA, Abramson E, Pfeiffer ME, Mills EM (2009) Chapter 70: Toxicology of Skeletal Muscle General and Applied Toxicology 3rd Ed. Wiley, ISBN#978-470-72327-2

Mills EM, Weaver KL, Abramson E, Pfeiffer M, Sprague JE (2008) Influence of dietary fats on ecstasy-induced hyperthermia Brit J Pharmacol 151: 1103-1108

SARA NOWINSKI
Graduate Student
College of Pharmacy
Email: sholdwick@mail.utexas.edu

Malignant cells display whole scale bioenergetic changes compared to normal cells that are typified by increased glycolysis and decreased mitochondrial oxidative phosphorylation / respiration.  Recent evidence suggests that this phenotype promotes the use of mitochondria as biosynthetic machines for cancer cell growth.  To better understand the relationships between changes in mitochondrial metabolism and carcinogenesis, our lab generated hemizygous mice expressing a skin-targeted uncoupling protein 3 construct that show increased cutaneous respiration and potent cancer resistance.  My project is focused on the mechanisms by which UCP3 antagonizes skin cancer development.

Education:
B.A. Biology (minor Biochemistry), Carleton College, Northfield, MN

CHRISTINE DAO
Rotating Graduate Student
College of Pharmacy
Email: kylinhdao@gmail.com

Heat shock proteins (HSPs) are involved in the cellular response to noxious stimuli such as toxicity, oxidative stress, hyperthermia and inflammation.  A recently characterized mitochondrial HSP named cvHSP is expressed most highly in the heart, skeletal muscle, and adipose tissues.  My project focuses on exploring the physiological role of HSP with specific emphasis on protein-protein interactions with mitochondrial proteins and its effects on mitochondrial metabolism.

Education:
B.S. Biology, Rice University, Houston, TX