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Michael Miller, PhD

Michael Miller, PhD
Department of Cell, Developmntl, & Integrative Biology
THT 952 Zip 0006
Phone: 205-934-9684

Michael A. Miller (b. 1971) received his Ph.D. in 1999 from the University of California at Irvine in the Department of Biological Chemistry. His postdoctoral training was done in David Greenstein’s lab at Vanderbilt University in the Department of Cell & Developmental Biology. He joined the UAB Department of Cell Biology in 2003 and was appointed to Associate Professor with tenure in 2009.

Research/Clinical Interest

Function and evolution of intercellular communication mechanisms
Multicellular organisms depend on intercellular communication or signaling mechanisms to coordinate the movement, differentiation, and proliferation of their cells. In humans, aberrant regulation of cell communication is the basis for many types of cancer, inflammatory disease, neurological disease, and infertility. Studies of distantly related animals are consistent with the hypothesis that a core, but incompletely discovered set of signaling mechanisms is used reiteratively during development to control basic cellular functions. We primarily use the nematode Caenorhabditis elegans as a simple in vivo model for discovering fundamental signaling mechanisms and elucidating their mechanisms of action. Our current focus is on two hormone classes critical for reproduction, lipid hormones called prostaglandins and protein hormones called MSPs. These two hormones mediate communication between sperm and egg that controls sperm motility and oocyte meiotic maturation, respectively. Prostaglandins are the targets of non-steroidal anti-inflammatory drugs, such as aspirin and ibuprofen. MSPs comprise a recently discovered, widespread class that bind to Eph receptors and other receptors. The human genome encodes fourteen Eph receptors, which are broadly expressed and implicated in vascular development, stem cell proliferation, nervous system functions, and oncogenesis. A point mutation in the VAPB MSP domain causes amyotrophic lateral sclerosis and late-onset spinal muscular atrophy, two neurodegenerative disorders. Research projects aim to discover biological roles of MSPs and prostaglandins, to determine how these hormones function, and to investigate their evolutionary origins.

Selected Publications

  • Han, S. M., Tsuda, H., Yang, Y., Vibbert, J., Cottee, P., Lee, S., Winek, J., Haueter, C., Bellen, H. J., and Miller, M. A. 2012. Secreted VAPB/ALS8 major sperm protein domains modulate mitochondrial localization and morphology via growth cone guidance receptors. Developmental Cell, 22:348-263. Cover article. Preview by Long and Van Vactor (pgs. 238-239). Featured in Birmingham News (front page), National Public Radio (WCUR Up to Date), New Scientist, and Alzheimer Research Forum. Evaluated in F1000.  22264801 
  • Edmonds, J. W., McKinney, S., Prasain, J. K., and Miller, M. A. (2011). The Gap Junctional Protein INX-14 Functions in Oocyte Precursors to Promote C. elegans Sperm Guidance. Developmental Biology, 359: 47-58.  21889935  
  • Edmonds, J. W., Prasain, J. K., Dorand, D., Yang, Y., Hoang, H., Vibbert, J., Kubagawa, H. M., and Miller, M. A. (2010). Insulin/FOXO Signaling Regulates Ovarian Prostaglandins Critical for Reproduction. Developmental Cell, 19:858-71. Reviewed by Faculty of 1000. 21145501 
  • Yang, Y., Han, S. M., and Miller, M. A. (2010). MSP Hormonal Control of the Oocyte MAP Kinase Cascade and Reactive Oxygen Species Signaling. Developmental Biology, 342:96-107. 20380830 
  • Han, S. M., Cottee, P., and Miller, M. A. (2010). Sperm and oocyte communication mechanisms controlling C. elegans fertility. Developmental Dynamics, 239:1265-81. 20034089  
  • Tsuda, H., Han, S. M., Yang, Y., Tong, C., Lin, Q. L., Mohan, K., Haueter, C., Zoghbi, A., Harati, Y., Kwan, J., Miller, M. A., and Bellen, H. J. (2008). The Amyotrophic Lateral Sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell, 133:963-77. On the cover. Preview by Ackerman and Cox. Reviewed by Faculty of 1000. 18555774 
  • Kubagawa, H., Watts, J., Corrigan, C., Edmonds, J., Sztul, E., Browse, J., and Miller, M. A. (2006). Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo. Nature Cell Biology, 8:1143-1148.  On the Cover. Featured in Nature Research Highlights, Oct. 12 issue. 16998478 
  • Whitten, S. and Miller, M. A. (2007). The role of gap junctions in Caenorhabditis elegans oocyte meiotic maturation and fertilization. Developmental Biology, 301:432-446.  16982048 
  • Corrigan, C., Subramanian, R., and Miller, M. A. (2005). Eph and NMDA receptors control Ca2+/calmodulin-dependent protein kinase II activation during C. elegans oocyte meiotic maturation. Development, 132: 5225-5237. 16267094 
  • Miller, M. A., Cutter, A. D., Yamamoto, I., Ward, S. and Greenstein, D. (2004). Clustered organization of reproductive genes in the C. elegans genome. Current Biology, 14: 1284-1290. 15268860 
  • Miller, M. A., Ruest, P., Kosinki, M., Hanks, S. and Greenstein, D. (2003). An Eph receptor sperm–sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans. Genes & Development, 17:187-200. On the Cover. Commentary by P. Kuwabara. 12533508 
  • Miller, M. A., Nguyen, V., Lee, M., Kosinski, M., Schedl, T., Caprioli, R. and Greenstein, D. (2001). A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation. Science, 291:2144-2147. Perspectives by A. Villeneuve. 11251118 
  • Miller, M. A., Malik, I., Shenk, M., and Steele, R. E. (2000). The Src/Csk regulatory circuit arose early in metazoan evolution. Oncogene, 19: 3925-3930. 10951585 
  • Miller, M. A., Technau, U., Smith, K. and Steele, R. E. (2000). Oocyte development in Hydra involves selection from competent precursor cells. Developmental Biology, 224: 326-338. 10926770 
  • Miller, M. A. and Steele, R. E. (2000). Lemon encodes an unusual receptor protein-tyrosine kinase expressed during gametogenesis in Hydra. Developmental Biology, 224: 286-298. 10926767