department of pharmacology

Beata Jastrzebska, Ph.D.

Beata Jastrzebska, PhD

Assistant professor

Phone: 216.368.5683
Fax: (216) 368-1300
E-mail: beata.jastrzebska@case.edu
W343B








Research:

Beata Jastrzebska, PhD

Signaling complexes of rhodopsin and the role of rhodopsin oligomeric organization in signal transduction

Research in Jastrzebska's lab focuses on understanding the structure and function of the visual G protein coupled receptor (GPCR), rhodopsin. In particular, we are interested in delineating of the rhodopsin supramolecular organization and its implications for the binding with the cognate heterotrimeric G protein, transducin. Rhodopsin is not only a fundamental molecule in our visual system that transmits the light signal to the brain, but it also is associated with diseases affecting human eyesight, including retinitis pigmentosa, retinal degeneration and night blindness. Several mutations identified in the rhodopsin gene leading to the retinal degeneration in humans, such as retinitis pigmentosa (RP), could affect membrane oligomeric organization of this receptor. Therefore, efforts are directed towards understanding the molecular basis of these inherited impairments using biochemical, biophysical and structural methods.

Molecular bases of light-induced retinal degeneration.

Additional areas of research in the laboratory include investigation of the underlying molecular mechanisms of the retinal degenerative diseases associated with compromised rhodopsin regeneration. The animal visual receptor rhodopsin is composed of an apoprotein opsin covalently bound to the vitamin A-derived chromophore, 11-cis-retinal. Rhodopsin activation includes chromophore isomerization to its all-trans stereoisomer, its subsequent release and recycling in a series of enzymatic reactions called the 'retinoid or visual' cycle. Dysfunction of enzymes involved in this cycle can impair rhodopsin regeneration and affect visual function. Regeneration of rhodopsin is compromised in several retinal disorders. Consequently, accumulated constitutively active, free opsin accelerates retinal degeneration. Novel, non-hydrolysable chromophore analogs are tested in context of potential therapeutic strategy to protect retinal health in these visual impairments. The effects of selected retinal analogs are tested in vitro and in vivo, in model animals.

Publications:

  • B. Jastrzebska, W.D. Comar, M.J. Kaliszewski, K.C. Skinner, M.H. Torcasio, A.S. Esway, H.  Jin, K. Palczewski and A.W. Smith (2017). A GPCR dimerization interface in human cone opsins. Biochemistry, 56(1):61-72. Cover story.
  • B. Jastrzebska, Y. Chen, T. Orban, H. Jin, L. Hofmann and K. Palczewski (2015). Disruption of rhodopsin dimerization with synthetic peptides targeting an interaction interface. Biol Chem. 290:25728-44.
  • B. Jastrzebska* (2015). Preface. Methods Mol. Biol., 1271:v-iv.
  • B. Jastrzebska* (2015). Oligomeric state of rhodopsin within rhodopsin-transducin complex probed with succinylated concanavalin a. Mol. Biol., 1271:221-33.
  • W.D. Comar, S.M. Schubert, B. Jastrzebska, K. Palczewski, and A.W. Smith (2014). Mobility and clustering of the opsin G protein-coupled receptor in live cells with time-resolved fluorescence spectroscopy. JACS, 136: 8342-9.
  • B. Jastrzebska* (2013). GPCR: G-protein complexes – the fundamental signaling assembly. Amino Acids, 45: 1303-14.
  • B. Jastrzebska*, P. Ringler, K. Palczewski and A. Engel (2013). The rhodopsin-transducin complex houses two distinct rhodopsin molecules. J. Struct. Biol., 182: 164-72.
  • B. Jastrzebska*, T. Orban, M. Golczak, A. Engel and K. Palczewski (2013). Asymmetry of the rhodopsin dimer in complex with transducin. FASEB J.,27: 1572-84.
  • B. Jastrzebska, D. Salom, H. Jin, P. Cao, W. Sun, K. Palczewski, and Z. Feng (2013). Expression of mammalian G protein-coupled receptors in Caenorhabditis elegans. Methods Enzymology, 520, 239-56.

Post-doctoral Candidates:

Interested candidates please send CV, brief statement of research interests, and list of references to Beata Jastrzebska (bxj27@case.edu).

Graduate Students:

Current Case Western Reserve University graduate students are encouraged to contact Beata Jastrzebska (bxj27@case.edu) to discuss potential rotation projects in the laboratory.