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Mala V. Rao, PhD

Research Assistant Professor, Department of Psychiatry

Summary
The major focus of my lab is to understand molecular cues that control the radia l growth of axons and death of motor neurons. Radial growth of axons is studied in mice by ES cell mediated homologous recombination. Motor neurons disease is s tudied in mouse models of amyotrophic lateral sclerosis (ALS) in transgenic mice for neurofilaments and superoxide dismutase 1 (SOD1). During development, axons undergo two major changes. First, the long, thin axons make growth cones and establish stable synapses. Second, axonal volume increase s 100 fold, and large myelinated axons accumulate large numbers of neurofilament s (NFs). NFs are 10 nm filaments composed of NF-H (200 kd), NF-M (150 kd) and N F-L (68 kd) subunits. Genetic analysis has shown a direct correlation between t he number of filaments and axonal volume. Our transgenic mouse models have indi cated that subunit ratios play a critical role in controlling radial growth of a xons. Recent gene deletion analysis on individual subunits indicate that NF-L i s important for filament formation; NF-M is important for filament assembly and control of filament number. In order to identify the domains of NF subunits tha t are responsible for controlling the radial growth of axons, a systematic domai n deletion approach is being used. We have successfully produced mice for carbox yl terminal deletions of NF-M and NF-H, and analyses of these mice are in progre ss. Approximately 2% of human ALS patients have mutations in the gene encoding for S OD1. A hallmark of ALS is neurofilament accumulation in cell bodies and proxima l axons. Over 50 mutations in SOD1 have been identified in human ALS patients. A large number of mouse models exist for ALS. The role of each NF subunit in d isease onset and progression of motor neuron death is unknown. In order to addr ess this question, NF-H deleted and over-expressing mice are bred with SOD1 over -expressing mice and efforts are underway to characterize these mice. Results will indicate the role of NF-H in motor neuron-mediated cell death.
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PhD from Indian Institute of Science

Rao, Mala V; Darji, Sandipkumar; Stavrides, Philip H; Goulbourne, Chris N; Kumar, Asok; Yang, Dun-Sheng; Yoo, Lang; Peddy, James; Lee, Ju-Hyun; Yuan, Aidong; Nixon, Ralph A

Autophagy. 2022 Sep 21; 1-16

Lee, Ju-Hyun; Yang, Dun-Sheng; Goulbourne, Chris N; Im, Eunju; Stavrides, Philip; Pensalfini, Anna; Chan, Han; Bouchet-Marquis, Cedric; Bleiwas, Cynthia; Berg, Martin J; Huo, Chunfeng; Peddy, James; Pawlik, Monika; Levy, Efrat; Rao, Mala; Staufenbiel, Mathias; Nixon, Ralph A

Nature neuroscience. 2022 Jun; 25(6):688-701

Lee, Ju-Hyun; Rao, Mala V; Yang, Dun-Sheng; Stavrides, Philip; Im, Eunju; Pensalfini, Anna; Huo, Chunfeng; Sarkar, Pallabi; Yoshimori, Tamotsu; Nixon, Ralph A

Autophagy. 2019 Mar; 15(3):543-557

Yuan, Aidong; Sershen, Henry; Basavarajappa, Balapal S; Smiley, John F; Hashim, Audrey; Bleiwas, Cynthia; Berg, Martin; Guifoyle, David N; Subbanna, Shivakumar; Darji, Sandipkumar; Kumar, Asok; Rao, Mala V; Wilson, Donald A; Julien, Jean-Pierre; Javitt, Daniel C; Nixon, Ralph A

Translational psychiatry. 2018 08 24; 8(1):167

Yuan, Aidong; Rao, Mala V; Veeranna; Nixon, Ralph A

Cold Spring Harbor perspectives in biology. 2017 Apr 03; 9(4):

Rao, Mala V; Campbell, Jabbar; Palaniappan, Arti; Kumar, Asok; Nixon, Ralph A

Journal of neurochemistry. 2016 Apr; 137(2):253-65

Correction to: Impact of nonoptimal intakes of saturated, polyunsaturated, and trans fat on global burdens of coronary heart disease. [J Am Heart Assoc. (2016) 5, e002891.] Doi:10.1161/JAHA.115.002891

Wang, Q; Afshin, A; Yakoob, M Y; Singh, G M; Rehm, C D; Khatibzadeh, S; Micha, R; Shi, P; Mozaffarian, D; Ezzati, M; Fahimi, S; Wirojratana, P; Powles, J; Elmadfa, I; Rao, M; Alpert, W; Lim, S S; Engell, R E; Andrews, K G; Abbott, P A; Abdollahi, M; Abeya, Gilardon E O; Ahsan, H; Al, Nsour M A A; Al-Hooti, S N; Arambepola, C; Fernando, D N; Barennes, H; Barquera, S; Baylin, A; Becker, W; Bjerregaard, P; Bourne, L T; Capanzana, M V; Castetbon, K; Chang, H -Y; Chen, Y; Cowan, M J; Riley, L M; De, Henauw S; Ding, E L; Duante, C A; Duran, P; Barbieri, H E; Farzadfar, F; Hadziomeragic, A F; Fisberg, R M; Forsyth, S; Garriguet, D; Gaspoz, J -M; Gauci, D; Calleja, N; Ginnela, B N V; Guessous, I; Gulliford, M C; Hadden, W; Haerpfer, C; Hoffman, D J; Houshiar-Rad, A; Huybrechts, I; Hwalla, N C; Ibrahim, H M; Inoue, M; Jackson, M D; Johansson, L; Keinan-Boker, L; Kim, C -I; Koksal, E; Lee, H -J; Li, Y; Lipoeto, N I; Ma, G; Mangialavori, G L; Matsumura, Y; McGarvey, S T; Fen, C M; Monge-Rojas, R A; Musaiger, A O; Nagalla, B; Naska, A; Ocke, M C; Oltarzewski, M; Szponar, L; Orfanos, P; Ovaskainen, M -L; Tapanainen, H; Pan, W -H; Panagiotakos, D B; Pekcan, G A; Petrova, S; Piaseu, N; Pitsavos, C; Posada, L G; Sanchez-Romero, L M; Selamat, R B T; Sharma, S; Sibai, A M; Sichieri, R; Simmala, C; Steingrimsdottir, L; Swan, G; Sygnowska, E H; Templeton, R; Thanopoulou, A; Thorgeirsdottir, H; Thorsdottir, I; Trichopoulou, A; Tsugane, S; Turrini, A; Vaask, S; van, Oosterhout C; Veerman, J L; Verena, N; Waskiewicz, A; Zaghloul, S; Zajkas, G

Journal of the American Heart Association. 2016 Jan 01; 5(1):1-1

Yuan, A; Sershen, H; Veeranna; Basavarajappa, B S; Kumar, A; Hashim, A; Berg, M; Lee, J-H; Sato, Y; Rao, M V; Mohan, P S; Dyakin, V; Julien, J-P; Lee, V M-Y; Nixon, R A

Molecular psychiatry. 2015 Aug; 20(8):986-94