Faculty Profile: Anita L. Zimmerman, Ph.D., University of Miami Medical School, 1982

Anita L. Zimmerman
Anita L. Zimmerman, Ph.D., University of Miami Medical School, 1982
Professor and Vice Chair
Molecular Pharmacology, Physiology & Biotechnology
Work: +1 401-863-2224
Our research is in molecular and cellular aspects of the nervous system, with an emphasis on ion channels and phototransduction in the eye and skin. Ion channels are membrane proteins that are critically involved in functions as diverse as the beating of the heart, visual perception, learning and memory, and hormone secretion. They are also targets for many drugs, and genetic defects in ion channels can cause devastating diseases, such as cystic fibrosis.

Biography

Dr. Zimmerman received a BS in Zoology in 1978 at the University of California, Berkeley, and a PhD in Physiology & Biophysics in 1982 at the University of Miami Medical School, with advisors Dr. Birgit Rose and Dr. Karl Magleby. Her PhD thesis project was on the mechanism of cell-to-cell communication via gap junctions. Before arriving at Brown in 1987, she obtained postdoctoral training with Dr. Denis Baylor in Neurobiology at Stanford Medical School, where she began studying ion channels and visual transduction in rods and cones. At Brown, she has continued to study ion channel biophysics, regulation and function in sensory transduction. Dr. Zimmerman teaches cellular neurophysiology and biophysics to medical students, as well as to graduate and undergraduate students. She is Professor and Vice Chair of Molecular Pharmacology, Physiology & Biotechnology (MPPB), and Director of the Graduate Program in Molecular Pharmacology & Physiology.

Institutions

Bu

Research Description

Research in my laboratory is in the area of molecular & cellular neurobiology. We study the function and regulation of ion channels and their role in sensory transduction and brain function. Essentially every function in the body is controlled by the activity of ion channels, which are membrane proteins that change their conformation in response to chemical and electrical signals, allowing specific ions to enter or exit cells as needed. Ion channels are critically involved in functions as diverse as nerve impulses in the brain, the beating of the heart, visual perception, muscle contraction, learning and memory, hormone secretion and embryonic development. They are also the targets of many drugs, such as those used to treat pain and heart disease; and genetic defects in ion channels can cause devastating diseases, such as cystic fibrosis. Our work centers mainly on nonselective cation channels that are opened by direct interaction with cyclic nucleotides (CNG channels), by other intracellular messengers (TRP channels) and by voltage (HCN channels). Since these particular ion channels contain pores that allow the passage of Ca2+ and Na+ into cells, their activity tends to make the membrane potential more positive and to increase intracellular Ca2+ levels, leading to cell excitation and triggering a variety of cell functions.

We use molecular biology and patch clamp (electrophysiology) techniques to record from channels in their native membranes and cells, as well as in heterologous expression systems (e.g., Xenopus frog eggs expressing cloned ion channels). My current work focuses on collaborations with Drs. Elena Oancea (Brown/MPPB) and Clint Makino (Harvard Medical School/Ophthalmology/Massachusetts Eye and Ear Infirmary). These collaborative projects center on UV signal transduction in the skin and visual transduction in retinal rods and cones, respectively.

Grants and Awards

1998-2001 Elected Member of the General Council of the Biophysical Society

1998-2001 Elected Member of Council for the Society of General Physiology.

2002 and 2004-2012: Dean's Excellence in Teaching Award for outstanding teaching in the first-year medical curriculum.

2006-present Member, Editorial Board, Journal of General Physiology

2011 Brown Graduate School Faculty Award for Advising and Mentoring.

2011-present Member, NST-2 study section, NIH/NINDS

Affiliations

Association for Research in Vision and Ophthalmology
Biophysical Society
Society of General Physiologists
Society for Neuroscience

Funded Research

Current grant:

NIH NIAMSD 1 R01 AR066318-01 (Co-PI; Dr. Elena Oancea is PI)
9/1/13-8/31/18
Ion channel and calcium signaling in ultraviolet light transduction in human skin.

Past grants and awards:

1988-2007: NIH research grant, R01 EY07774 (National Eye Institute), "Properties of light-modulated ion channels in the retina."

1998: Salomon Faculty Research Award, "Molecular mechanism of modulation of cyclic nucleotide-gated ion channels by Ca2+/calmodulin."

1998: Rhode Island Foundation Research Grant, "Molecular mechanism of modulation of cyclic nucleotide-gated ion channels by Ca2+/calmodulin."

1997-1999: RI American Heart, "Modulation of ion channels in the sino-atrial node of the heart."

2007-2008: Maren Foundation Award for equipment, "Request for equipment for a novel tissue preparation to study vision."

2007-2008: Maren Research Seed Award from MPPB, "The RPE/retinal slice: a new preparation for studying photoreceptor responses to bright light in health and disease."

2009: Brown Advance Scientific Leadership Award.

Teaching Experience

Cellular physiology sections of first-year medical school course, BIOL 3642; cardiac cell physiology in second-year medical school course, BIOL 3662.

Cellular physiology section of MPP graduate core course, BIOL 2170.

Course director and lecturer in cell physiology, ion channel biophysics and other topics in BIOL 1100.

Guest lectures on ion channel physiology and biophysics in other courses, especially in Physics and Neuroscience.

Courses Taught

  • Cell Physiology and Biophysics (BIOL 1100)
  • Integrated Medical Sciences I: Scientific Foundations of Medicine (BIOL 3642)
  • Integrated Medical Sciences III: Cardiovascular (BIOL 3662)
  • Molecular Pharmacology and Physiology Seminar (BIOL 2940A)
  • Receptor, Channels and Signaling (BIOL 2170)

Selected Publications

  • Bellono, N.W., Kammel, L.G., Zimmerman, A.L. and Oancea, E. UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes. Proc. Natl. Acad. Sci. USA. 110: 2383-2388 (2013); Epub, Jan 23, 2013. PMCID: PMC3568351 (2013)
  • Khan, S., Perry, C., Tetreault, M.L., Henry, D., Trimmer, J.S., Zimmerman, A.L. and Matthews, G. A novel cyclic nucleotide-gated ion channel enriched in synaptic terminals of isotocin neurons in zebrafish brain and pituitary. Neuroscience 165: 79-89 (2010). (2010)
  • Isayama, T., McCabe England, S.L., Crouch, R.K., Zimmerman, A.L. and Makino, C.L. Beta-ionone activates and bleaches visual pigment in salamander photoreceptors. Visual Neuroscience 26: 267-274 (2009). (2009)
  • Zimmerman, A.L. The sweet smell of success: conclusive evidence that cyclic AMP hydrolysis does not trigger fast adaptation in olfactory receptor cells. J. Gen. Physiol. 128: 149-151 (2006). Invited paper, but reviewed. (2006)
  • Tetreault, M.L., Horrigan, D.M., Kim, J.A. and Zimmerman, A.L. Retinoids restore normal cGMP sensitivity of mutant ion channels associated with cone dystrophy. Molecular Vision 12: 1699-1705 (2006). (2006)
  • Tetreault, M.L., Henry, D., Horrigan, D.M., Matthews, G. and Zimmerman, A.L. Characterization of a novel cyclic nucleotide-gated channel from zebrafish brain. Biochem. Biophys. Res. Comm. 348: 441-449 (2006). (2006)
  • He, Q., Alexeev, D., Estevez, M.E., McCabe, S.L., Calvert, P.D., Ong, D.E., Cornwall, M.C., Zimmerman, A.L. and Makino, C.L. Cyclic nucleotide-gated ion channels in rod photoreceptors are protected from retinoid inhibition. J. Gen. Physiol. 128: 473-485 (2006). (2006)
  • Horrigan, D.M., Tetreault, M.L., Tsomaia, N., Vasileiou, C., Borhan, B., Mierke, D.F., Crouch, R.K. and Zimmerman, A.L. Defining the retinoid binding site in the rod cyclic nucleotide-gated channel. J. Gen. Physiol. 126: 453-460 (2005). (2005)
  • Yeh, J.I., Zimmt, M. B., and Zimmerman, A. L. Nanowiring of a Redox Enzyme by Metallized Peptides. Rapid communication, Biosensors & Bioelectronics 21: 973-978 (2005). (2005)
  • Zimmerman, A.L. Capturing ion channel gating: a little salt on the tail does the trick. J. Gen. Physiol. 124: 627-629 (2004). Invited paper, but reviewed. (2004)
  • McCabe, S.L., Pelosi, D.M., Tetreault, M., Miri, A., Nguitragool, W., Kovithvathanaphong, P., Mahajan, R. and Zimmerman, A.L. All-trans-retinal is a closed-state inhibitor of rod cyclic nucleotide-gated ion channels. J. Gen. Physiol. 123: 521-531 (2004). (2004)
  • Zimmerman, A.L. Two B or not two B? Questioning the rotational symmetry of tetrameric ion channels. Neuron 36: 997-999 (2002). This was an invited, but peer-reviewed, minireview. (2002)
  • Dean, D.M., Nguitragool, W., Miri, A., McCabe, S.L. and Zimmerman, A.L. All-trans-retinal shuts down rod cyclic nucleotide-gated ion channels: a novel role for photoreceptor retinoids in the response to bright light? Proc. Natl. Acad. Sci. USA 99: 8372-8377 (2002). (2002)
  • Crary, J.I., Dean, D.M., Maroof, F. and Zimmerman, A.L. Mutation of a single residue in the S2-S3 loop of CNG channels alters the gating properties and sensitivity to inhibitors. J. Gen. Physiol. 116: 769-779 (2000). (2000)
  • Crary, J.I., Dean, D.M., Nguitragool, W., Kurshan, Peri T. and Zimmerman, A.L. Mechanism of Inhibition of Cyclic Nucleotide-Gated Ion Channels by Diacylglycerol. J. Gen. Physiol. 116: 755-768 (2000). (2000)
  • Crary, J.I., Gordon, S.E. and Zimmerman, A.L. Perfusion system components release agents that distort functional properties of rod cyclic nucleotide-gated ion channels. Visual Neuroscience 15: 1189-1193 (1998). (1998)
  • Zimmerman, A.L. Visual transduction. In: Cell Physiology Source Book: A Molecular Approach (Essentials of Membrane Biophysics is the new subtitle for 4th edition, 2012). N. Sperelakis, editor. Academic Press (chapter 37 in 1st edition, 1995; chapter 47 in 2nd edition, 1998; chapter 48 in 3rd edition, 2001; Chapter 38 in 4th edition, 2012). (1995)
  • Zimmerman, A.L. Cyclic nucleotide gated ion channels. In: Cell Physiology Source Book: A Molecular Approach (Essentials of Membrane Biophysics is the new subtitle for 4th edition, 2012). N. Sperelakis, editor. Academic Press (chapter 36 in 1st edition, 1995; chapter 46 in 2nd edition, 1998; chapter 47 in 3rd edition, 2001, Chapter 35 in 4th edition, 2012). (1995)
  • Gordon, S.E., Downing-Park, J., Tam, B. and Zimmerman, A.L. Diacylglycerol analogs inhibit the rod cGMP-gated channel by a phosphorylation-independent mechanism. Biophys. J. 69: 409-417 (1995). (1995)
  • Gordon, S.E., Downing-Park, J. and Zimmerman, A.L. Modulation of the cGMP-gated ion channel in frog rods by calmodulin and an endogenous inhibitory factor. J. Physiol. 486: 533-546 (1995). (1995)
  • Zimmerman, A.L. Cyclic nucleotide-gated channels. Current Opinion in Neurobiology 5: 296-303 (1995). (1995)
  • Gordon, S.E., Brautigan, D.L. and Zimmerman, A.L. Protein phosphatases modulate the apparent agonist affinity of the light-regulated ion channel in retinal rods. Neuron 9: 739-748 (1992). (1992)
  • Zimmerman, A.L. and Baylor, D.A. Cation interactions within the cyclic GMP-activated channel of retinal rods from the tiger salamander. J.Physiol. 449: 759-783 (1992). (1992)
  • Zimmerman, A.L., Karpen, J.W., Kantrowitz-Gordon, S., Tsai, C-S. S., Baylor, D.A. and Stryer, L. Workings of the cGMP-activated channels of retinal rods. Neuroscience Research, Suppl. 12, S165 - S174 (1990). (1990)
  • Karpen, J.W., Zimmerman, A.L., Stryer, L., and Baylor, D.A. Molecular mechanics of the cyclic GMP-activated channel of retinal rods. In: Cold Spring Harbor Symposium on Quantitative Biology, Vol. 53 (1988). (1988)
  • Zimmerman, A.L., Karpen, J.W. and Baylor, D.A. Hindered diffusion in excised membrane patches from retinal rod outer segments. Biophys. J. 54: 351-355 (1988). (1988)
  • Karpen, J.W., Zimmerman, A.L., Stryer, L. and Baylor, D.A. Gating kinetics of the cyclic-GMP-activated channel of retinal rods: flash photolysis and voltage-jump studies. Proc. Natl. Acad. Sci. USA. 85: 1287-1291 (1988). (1988)
  • Zimmerman, A.L. and Baylor, D.A. The cyclic GMP-sensitive conductance of retinal rods consists of aqueous pores. Nature 321: 70-72 (1986). (1986)
  • Zimmerman, A.L., Yamanaka, G., Eckstein, F., Baylor, D.A. and Stryer, L. Interaction of hydrolysis-resistant analogs of cyclic GMP with the phosphodiesterase and light-sensitive channel of retinal rod outer segments. Proc. Natl. Acad. Sci. USA 82: 8813-8817 (1985). (1985)
  • Zimmerman, A.L. and Rose, B. Permeability properties of cell-to-cell channels: Kinetics of fluorescent tracer diffusion through a cell junction. J. Membrane Biol. 84: 269-283 (1985). (1985)
  • Tedeschi, B., Wilson, D.L., Zimmerman, A.L. and Perry, G.W. Are axonally transported proteins released from sciatic nerves? Brain Research 211: 175-178 (1981). (1981)
  • Schwarzmann, G., Weigandt, H., Rose, B., Zimmerman, A.L., Ben-Haim, D. and Loewenstein, W.R. Diameter of the cell-to-cell junctional membrane channels as probed with neutral molecules. Science 213: 551-553 (1981). (1981)
  • Jensen, R.H., Bigbee, W.L., Zimmerman, A.L. and King, E.B. Plasminogen activator as a diagnostic marker for preneoplastic cells in human gynecologic specimens. Acta Cytol. 23: 105 (1979). (1979)
  • Zimmerman, A.L., King, E.B., Barrett, D.L. and Petrakis, N.L. The incidence and significance of intracytoplasmic calcifications in nipple aspirate specimens. Acta Cytol. 21: 685-692 (1977). (1977)
  • King, E.B., Zimmerman, A.L., Barrett, D.L., Petrakis, N.L. and King, M.C. Cytopathology of abnormal mammary duct epithelium. In: Proceedings of the Third International Symposium on Detection and Prevention of Cancer. New York, April 29, 1976. (1976)