""

about | Maps & Directions | contact | admissions | faculty | alumni & development | library | Tech Support Center | dean's office | Policies & Procedures

FAculty directory

Back to alphabetical index

 

Brad Rothberg, PhDBrad S. Rothberg, PhD

 

Associate Professor, Biochemistry

Telephone:  215-707-0855

Fax:  215-707-7536

Email: rothberg@temple.edu

 

Department of Biochemistry

 

Educational Background:

 

BS (Neuroscience), University of Pittsburgh, Pittsburgh, PA, 1987

 

PhD, University of Florida, Gainesville, FL, 1994

 

Postdoctoral fellowship, Physiology and Biophysics, University of Miami School of Medicine, Miama, FL, 1994-1999

 

Research fellow in Neurobiology, Harvard Medical School, Boston, MA, 1999-2002

 

Return to top

 

 

Research Interests:

 

Ion channels are a specialized class of proteins that form pores in cell membranes. Charged ions (such as sodium or potassium) can selectively flow through a channel's open pore, producing electrical current. The currents produced by the variety of ion channels in our cells and tissues gives rise to an important electrical component of cell signaling. The best known examples of this electrical signaling include the action potentials that we can observe in nerve and muscle.

 

Rothberg image

 

The research in my laboratory is aimed at figuring out how ion channels work at the molecular level. Our strategy to study channel structure and function combines patch-clamp electrophysiology, site-directed mutagenesis, fluorescence and NMR spectroscopy, X-ray crystallography and biochemical techniques to deduce a working hypothesis of the molecular architecture of a channel.


Our work is focused primarily on calcium-activated potassium channels. These types of channels are found in many organisms, ranging from bacteria and insects to humans. In higher organisms, the opening of these channels lets potassium flow out of the cell; this hyperpolarizes the cell membrane and decreases electrical excitability. In nerve cells, this translates to a decrease in action potential firing; in the smooth muscle cells that line blood vessels and the trachea, this translates to relaxation, so these channels may be therapeutic targets in the control of blood pressure and asthma.


We are interested in several fundamental questions. Which region of this channel is responsible for binding calcium? Which region of the channel controls the flow of ions through the pore, acting like a 'gate'? How do different parts of the channel talk to the gate, telling it when to open or close? We already know that the gates of an ion channel open only in the presence of the appropriate chemical or electrical signal, so by learning how different signals (like calcium) open and close the gates of channels, we can better understand how ion channels regulate electrical activity in different cell types.


My laboratory is fully equipped to perform patch clamp electrophysiology, site-directed mutagenesis and recombinant DNA techniques, fluorescence microscopy and spectroscopy, PAGE and western blotting, protein purification and crystallization, and lipid bilayer recording.

 

Return to top

 

 

LABORATORY PERSONNEL:

  • Karin Abarca-Heidemann, PhD, Associate Scientist
  • Victor P. T. Pau, PhD, Postdoctoral Fellow
  • Andrew S. Thomson, Biochemistry Graduate Student
  • Frank J. Smith, Biochemistry Graduate Student

Return to top

 

 

professional organizations:

 

  • Society for Neuroscience
  • Society of General Physiologists
  • The Biophysical Society

Return to top

 

 

award(s):

 

Lyndon B. Johnson Research Award, awarded by American Heart Association, Texas affiliate, 2002

Return to top

 

 

PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24733889. Thomson AS, Heer FT, Smith FJ, Hendron E, Bernèche S, Rothberg BS, Initial steps of inactivation at the K+ channel selectivity filter. Proc Natl Acad Sci U S A :()2014 Apr 14

24492416. Wang X, Wang Y, Zhou Y, Hendron E, Mancarella S, Andrake MD, Rothberg BS, Soboloff J, Gill DL, Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site. Nat Commun 5:(3183)2014

24126388. Smith FJ, Pau VP, Cingolani G, Rothberg BS, Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain. Nat Commun 4:(2621)2013

23529439. Abarca-Heidemann K, Duchardt-Ferner E, Woehnert J, Rothberg BS, Isotope labeling strategies for analysis of an ion channel cytoplasmic domain by NMR spectroscopy. Methods Mol Biol 998:(289-300)2013

23529438. Smith FJ, Rothberg BS, Analysis of Ca(2+)-binding sites in the MthK RCK domain by X-ray crystallography. Methods Mol Biol 998:(277-87)2013

23512988. Rothberg BS, Wang Y, Gill DL, Orai channel pore properties and gating by STIM: implications from the Orai crystal structure. Sci Signal 6:267(pe9)2013 Mar 19

23101630. Mallilankaraman K, Doonan P, Cárdenas C, Chandramoorthy HC, Müller M, Miller R, Hoffman NE, Gandhirajan RK, Molgó J, Birnbaum MJ, Rothberg BS, Mak DO, Foskett JK, Madesh M, MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell 151:3(630-44)2012 Oct 26

23085076. Smith FJ, Pau VP, Cingolani G, Rothberg BS, Crystal structure of a Ba(2+)-bound gating ring reveals elementary steps in RCK domain activation. Structure 20:12(2038-47)2012 Dec 5

22996175. Rothberg BS, The BK channel: a vital link between cellular calcium and electrical signaling. Protein Cell 3:12(883-92)2012 Dec

22914293. Soboloff J, Rothberg BS, Madesh M, Gill DL, STIM proteins: dynamic calcium signal transducers. Nat Rev Mol Cell Biol 13:9(549-65)2012 Sep

21997217. Pau VP, Smith FJ, Taylor AB, Parfenova LV, Samakai E, Callaghan MM, Abarca-Heidemann K, Hart PJ, Rothberg BS, Structure and function of multiple Ca2+-binding sites in a K+ channel regulator of K+ conductance (RCK) domain. Proc Natl Acad Sci U S A 108:43(17684-9)2011 Oct 25

20937694. Thomson AS, Rothberg BS, Voltage-dependent inactivation gating at the selectivity filter of the MthK K+ channel. J Gen Physiol 136:5(569-79)2010 Nov

20421375. Pau VP, Abarca-Heidemann K, Rothberg BS, Allosteric mechanism of Ca2+ activation and H+-inhibited gating of the MthK K+ channel. J Gen Physiol 135:5(509-26)2010 May

19244238. Semenova NP, Abarca-Heidemann K, Loranc E, Rothberg BS, Bimane fluorescence scanning suggests secondary structure near the S3-S4 linker of BK channels. J Biol Chem 284:16(10684-93)2009 Apr 17

19204188. Wang B, Rothberg BS, Brenner R, Mechanism of increased BK channel activation from a channel mutation that causes epilepsy. J Gen Physiol 133:3(283-94)2009 Mar

18955591. Rothberg BS, Return of the electric binding site. J Gen Physiol 132:5(487-9)2008 Nov

17588939. Parfenova LV, Abarca-Heidemann K, Crane BM, Rothberg BS, Molecular architecture and divalent cation activation of TvoK, a prokaryotic potassium channel. J Biol Chem 282:33(24302-9)2007 Aug 17

17296928. Koval OM, Fan Y, Rothberg BS, A role for the S0 transmembrane segment in voltage-dependent gating of BK channels. J Gen Physiol 129:3(209-20)2007 Mar

16929946. Parfenova LV, Rothberg BS, Genetic screening for functionality of bacterial potassium channel mutants using K+ uptake-deficient Escherichia coli. Methods Mol Biol 337:(157-65)2006

16728395. Parfenova LV, Crane BM, Rothberg BS, Modulation of MthK potassium channel activity at the intracellular entrance to the pore. J Biol Chem 281:30(21131-8)2006 Jul 28

16567466. Wang B, Rothberg BS, Brenner R, Mechanism of beta4 subunit modulation of BK channels. J Gen Physiol 127:4(449-65)2006 Apr

15069208. Rothberg BS, Allosteric modulation of ion channels: the case of maxi-K. Sci STKE 2004:227(pe16)2004 Mar 30

15003173. Shin KS, Maertens C, Proenza C, Rothberg BS, Yellen G, Inactivation in HCN channels results from reclosure of the activation gate: desensitization to voltage. Neuron 41:5(737-44)2004 Mar 4

14557404. Rothberg BS, Shin KS, Yellen G, Movements near the gate of a hyperpolarization-activated cation channel. J Gen Physiol 122:5(501-10)2003 Nov

11773240. Rothberg BS, Shin KS, Phale PS, Yellen G, Voltage-controlled gating at the intracellular entrance to a hyperpolarization-activated cation channel. J Gen Physiol 119:1(83-91)2002 Jan

11432375. Rothberg BS, Magleby KL, Testing for detailed balance (microscopic reversibility in ion channel gating. Biophys J 80:6(3025-6)2001 Jun

11158163. Shin KS, Rothberg BS, Yellen G, Blocker state dependence and trapping in hyperpolarization-activated cation channels: evidence for an intracellular activation gate. J Gen Physiol 117:2(91-101)2001 Feb

10871641. Rothberg BS, Magleby KL, Voltage and Ca2+ activation of single large-conductance Ca2+-activated K+ channels described by a two-tiered allosteric gating mechanism. J Gen Physiol 116:1(75-99)2000 Jul 1

10398695. Rothberg BS, Magleby KL, Gating kinetics of single large-conductance Ca2+-activated K+ channels in high Ca2+ suggest a two-tiered allosteric gating mechanism. J Gen Physiol 114:1(93-124)1999 Jul

9711623. Rothberg BS, Magleby KL, Investigating single-channel gating mechanisms through analysis of two-dimensional dwell-time distributions. Methods Enzymol 293:(437-56)1998

9607935. Rothberg BS, Magleby KL, Kinetic structure of large-conductance Ca2+-activated K+ channels suggests that the gating includes transitions through intermediate or secondary states. A mechanism for flickers. J Gen Physiol 111:6(751-80)1998 Jun

9168029. Rothberg BS, Bello RA, Magleby KL, Two-dimensional components and hidden dependencies provide insight into ion channel gating mechanisms. Biophys J 72:6(2524-44)1997 Jun

8986212. Rothberg BS, Hunter BE, Walker DW, Anderson JF, Anderson KJ, Long-term effects of chronic ethanol on muscarinic receptor binding in rat brain. Alcohol Clin Exp Res 20:9(1613-7)1996 Dec

8799891. Rothberg BS, Bello RA, Song L, Magleby KL, High Ca2+ concentrations induce a low activity mode and reveal Ca2(+)-independent long shut intervals in BK channels from rat muscle. J Physiol 493 ( Pt 3):(673-89)1996 Jun 15

8131051. Rothberg BS, Yasuda RP, Satkus SA, Wolfe BB, Hunter BE, Effects of chronic ethanol on cholinergic actions in rat hippocampus: electrophysiological studies and quantification of m1-m5 muscarinic receptor subtypes. Brain Res 631:2(227-34)1993 Dec 24

1784427. Rothberg BS, Hunter BE, Chronic ethanol treatment differentially affects muscarinic receptor responses in rat hippocampus. Neurosci Lett 132:2(243-6)1991 Nov 11

Return to top