Terry A. Krulwich
- PROFESSOR Pharmacology and Systems Therapeutics
M.S., Ph.D., NSF Predoctoral Fellowship, University of Wisconsin
NSF Postdoctoral Fellowship, Albert Einstein College of Medicine
B.A., Goucher College
Dr. Krulwich is the Sharon & Frederick A. Klingenstein-Nathan G. Kase, MD Professor, Program Director of the Mount Sinai Post-Baccalaureate Research Education Program and of the pre-doctoral Integrated Pharmacological Sciences Training Program. She is also Education and Outreach Core Director for the Systems Biology Center New York. Dr. Krulwich's research programs are described under the Krulwich Laboratory.
Summary of Research Interests
The Krulwich Laboratory studies ion-translocating membrane transporters in bacterial cells are critical participants in the physiology of both pathogens and non-pathogenic bacteria of ecological interest.
Oxidative phosphorylation at high pH: a model system for probing the proton path during energization of ATP synthesis by the respiratory chain. Biochemical, molecular and biophysical studies of OXPHOS in mutant and wild-type cells, membranes and purified systems test the hypothesis of sequestered proton transfer during OXPHOS that depend upon special adaptations of the ATP synthase and respiratory chain complexes and may also depend upon specific membrane phospholipid content. In collaboration with Thomas Meier’s research group (Max Planck Biophysics Institute, Frankfurt, Germany), structural studies of the ATP synthase rotor are unraveling properties that relate to specific adaptations of the alkaliphile synthase as well as properties that are likely to be found more broadly among bacterial ATP synthases.
Mrp-type monovalent cation/proton antiporter systems: basis and roles for the unusual complexity of this major bacterial antiporter system. In collaboration with Masahiro Ito's lab (Toyo University, Japan), we study the catalytic properties, physiological roles and structural features of Mrp systems from bacteria such as pathogenic Staphylococcus aureus and non-pathogenic Bacillus species. We are testing the hypothesis that Mrp proteins form a complex that is a "consortium" of transporters that includes monovalent cation/proton antiporters and which function synergistically. We are also investigating a systems response by bacterial cells in which stresses that lead to an acute increase in Mrp function, thereby acutely reducing the membrane potential that energizes antiport, sets in motion a series of events that leads to a membrane potential that is even higher than in the absence of the original stress(es).
Structure-function studies of the tetracycline efflux protein, TetL, that supports tetracycline-resistance in Gram-positive bacteria is being investigated with the goal of achieving information that will further define the catalytic capacities of the transporter and will inform design of inhibitors of the antibiotic-resistance protein. This work is part of a collaboration with Da-Neng Wang’s laboratory (Skirball Institute, NYU).
Dr. Krulwich also leads an NIH-supported educational study, together with Suman Saran (Project Manager) and a team of researchers from Mount Sinai, on factors that enhance the successful post-baccalaureate intervention to promote research careers and factors that prevent attrition of pre-doctoral students from under-represented and/or disadvantaged backgrounds (ESPI study). The hypotheses to be tested inthe ESPI study emerged from observations made during the initial period of Dr. Krulwich's directorship of Mount Sinai's Post-baccalaureate Research Education Program (Mount Sinai PREP).
Janto B, Ahmed A, Ito M, Liu J, Hicks DB, Pagni S, Fackelmayer OJ, Smith TA, Earl J, Elbourne LD, Hassan K, Paulsen IT, Kolstø AB, Tourasse NJ, Ehrlich GD, Boissy R, Ivey DM, Li G, Xue Y, Ma Y, Hu FZ, Krulwich TA. Genome of alkaliphilic Bacillus pseudofirmus OF4 reveals adaptations that support the ability to grow in an external pH range from 7.5 to 11.4. Environmental microbiology 2011 Dec; 13(12): 3289-3309.
Liu J, Fackelmayer OJ, Hicks DB, Preiss L, Meier T, Sobie EA, Krulwich TA. Mutations in a helix-1 motif of the ATP synthase c-subunit of Bacillus pseudofirmus OF4 cause functional deficits and changes in the c-ring stability and mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biochemistry 2011 Jun; 50(24): 5497-5506.
Krulwich TA, Sachs G, Padan E. Molecular aspects of bacterial pH sensing and homeostasis. Nature reviews. Microbiology 2011 May; 9(5): 330-343.
Hoffmann J, Sokolova L, Preiss L, Hicks DB, Krulwich TA, Morgner N, Wittig I, Schagger H, Meier T, Brutschy B. ATP synthases: cellular nanomotors characterized by LILBID mass spectrometry. Phys Chem Chem Phys 2010 Aug; 12(41): 13375-13382.
Fujisawa M, Fackelmayer O, Liu J, Krulwich TA, Hicks DB. The ATP synthase a-subunit of extreme alkaliphiles is a distinct variant. Mutations in the critical alkaliphile-specific residue Lys-180 and other residues that support alkaliphile OXPHOS. J Biol Chem 2010 Aug; 285(42): 32105-32115.
Preiss L, Yildiz O, Hicks DB, Krulwich TA, Meier T. A new type of proton coordination in an F(1)F(o)-ATP synthase rotor ring. PLoS Biol 2010 Aug; 8(8): e100443.
Morino M, Natsui S, Ono T, Swartz TH, Krulwich TA, Ito M. Single site mutations in the hetero-oligomeric Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4 that affect Na+/H+ antiport activity, sodium exclusion, individual Mrp protein levels or Mrp complex formation. J Biol Chem 2010 Oct; 285(40): 30942-30950.
Hicks DB, Liu J, Fujisawa F, Krulwich TA. F(1)F(0)-ATP synthases of alkaliphilic bacteria: Lessons from their adaptations. Biochim Biophys Acta 2010 Aug; 1797(8): 1362-1377.
Krulwich TA, Hicks DB, Ito M. Cation/proton antiporter complements of bacteria: why so large and diverse. Mol Microbiol 2009 Oct; 74(2): 257-260.
Liu J, Fujisawa M, Hicks DB, Krulwich TA. Characterization of the functionally critical AXAXAXA and PXXEXXP motifs of the ATP synthase c-subunit from an alkaliphilic Bacillus. J Biol Chem 2009 Mar; 284(13): 8714-8725.
Terahara N, Krulwich TA, Ito M. Mutations alter the sodium versus proton use of a Bacillus clausii flagellar motor and confer dual ion use on Bacillus subtilis motors. Proc Natl Acadm Sci U S A 2008 Sept; 105(38): 14359-14364.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Krulwich did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
Annenberg Building Floor 19 Room 19-36 (Lab)
1468 Madison Avenue
New York, NY 10029
Annenberg Building Floor 19 Room 19-24 (Office)
1468 Madison Avenue
New York, NY 10029