Jeffrey Brender

Biophysics 930 N. University Ave. Ann Arbor, MI 48109-1055 (734) 763-9318

Academic Training

Staff Scientist PI: Ayyalusamy Ramamoorthy 2009-Date University of Michigan

Postdoctoral Associate Mentor: Ayyalusamy Ramamoorthy 2006-2009 University of Michigan

Ph.D. in Biophysics Advisor: Duncan Steel and Ari Gafni 2000-2006 University of Michigan

Thesis: "The Use of Single-Molecule Detection in the Resolution of Complex Enzyme Kinetics"

B.S. in Honors Chemistry Advisor: Lawrence Lohr 1994-1999 University of Michigan, magna cum laude

Thesis: “Theoretical Analysis of Long-Range Electron Transfer in Blue-Copper Proteins”

Awarded Highest Distinction for a Chemistry Undergraduate Thesis

Research Interests

  • Membrane Biophysics
  • Amyloid Proteins and Protein Aggregation
  • Natively Unfolded Proteins and Denatured States of Proteins
  • Solid and Solution State NMR and Fluorescence Spectroscopic Techniques

Honors Received

  • 2004-2006 Graduate Fellowship, Institute of Gerontology Training Grant
  • 2002-2004 Graduate Fellowship, Molecular Biophysics Training Grant
  • 2000-2002 University of Michigan Regent’s Scholarship
  • 1999 Highest Distinction-Undergraduate Thesis in Chemistry
  • 1999 Graduated with High Honors, B.S Chemistry

Peer-reviewed publications (Over1000 citations, h index 18)

38. Lee, D.K., J.R. Brender, M.F.M. Sciacca, J. Krishnamoorth, C. Yu, and A. Ramamoorthy. Lipid Composition Dependent Detergent-Like and Pore-forming Mechanisms of Membrane Disruption by Pexiganan. In press

37. Hyung, S.J., A.S. DeToma, J.R. Brender, S. Lee, S. Vivekanandan, A. Kochi, A. Ramamoorthy, B.T. Ruotolo, and M. H. Lim. New Insights into the Anti-Amyloidogenic Properties of the Green Tea Extract: Metal-Free Versus Metal-Associated Aβ. Proc. Natl. Acad. Sci. U.S.A., 110: 3743-3748. Reviewed in F1000.

36. Brender, J.R., J. Krishnamoorthy, G.F.M. Messina, A. Deb, J. E. Penner-Hahn, S. Vivekanandan, C. La Rosa, and A. Ramamoorthy. Zinc Stabilization of Prefibrillar Oligomers of Human Islet Amyloid Polypeptide. Chem. Commun., 49: 3339-3341.

35. Brender J.R., D. L. Heyl, S. Samisetti, S. A. Kotler, J. M. Osborne, R. R. Pesaru, and A. Ramamoorthy. Membrane Disordering is not Sufficient for Membrane Permeabilization by Islet Amyloidogenic Polypeptide: Studies of IAPP(20-29) Fragments. Phys. Chem. Chem. Phys., In press.

34. Suzuki, Y. , J.R. Brender, M.T. Soper, J. Krishnamoorthy, Y. Zhou, N. A. Kotov, B.T. Ruotolo, A. Ramamoorthy, and E. N. G. Marsh. Resolution of Oligomeric Species during the Aggregation of Aβ1-40 Using 19F NMR. Biochemistry, 52: 1903-1912. Editor's Choice

33. Hartman, K., J.R. Brender, N. Popovych, M. R. Chapman, and A. Ramamoorthy. Bacterial Curli Protein Catalyzes the In Vitro Conversion of PAP(248-286) into the SEVI Amyloid Form. Peer J., In press.

32. Sciacca, M. F. M., D. Milardi, G. Messina, G. Marletta, J.R. Brender, A. 2013. Ramamoorthy, and C. La Rosa. Pores Versus Fibrils: Calcium Ions as Switches of Different IAPP-Mediated Membrane Damage Mechanisms. Biophys. J., 104: 173-184.

31. Krishnamoorthy, J., J. R. Brender, S.Vivekanandan, and A. Ramamoorthy. 2012. Side Chain Dynamics Reveals Transient Association of Aβ1-40 Monomers with Amyloid Fibers. J. Phys. Chem. B, 116: 13618-13623. Editor's Choice

30. Suzuki, Y., J. R. Brender, K. Hartman, A. Ramamoorthy, and E. N. G. Marsh. 2012. Alternative Pathways of Human Islet Amyloid Polypeptide Aggregation Distinguished by 19F NMR-Detected Kinetics of Monomer Consumption. Biochemistry, 51: 8154-8162.

29. Sciacca, M. F. M., J. R. Brender, D.K. Lee, and A. Ramamoorthy. 2012. Phosphatidylethanolamine Enhances Amyloid Fiber Dependent Membrane Fragmentation. Biochemistry, 51: 7676-7684.

28. Sciacca, M. F. M., S. A. Kotler, J. R. Brender, J. Chen,2 D. K. Lee, and A. Ramamoorthy. 2012. Two step mechanism of membrane disruption by Aβ through membrane fragmentation and pore formation. Biophys. J., 103: 702-710 (Featured article, most downloaded paper in August issue)

27. Brender J.R., A.J. McHenry, and A. Ramamoorthy. 2012. Does Cholesterol Play a Role in the Bacterial Selectivity of Antimicrobial Peptides? Front. Immunol., 3: 1-4. Invited review.

26. McHenry AJ, M.F.M. Sciacca, J.R. Brender, and A. Ramamoorthy. 2012. Does Cholesterol Suppress the Antimicrobial Peptide Induced Disruption of Lipid Raft Containing Membranes? Biochim. Biophys. Acta, Biomemb., 1818: 3019-3024.

25. Popovych, N., J.R. Brender, R. Soong, S. Vivekanandan, K. Hartman, P.M. Macdonald, and A. Ramamoorthy. 2012. Site Specific Interaction of EGCG with the SEVI Precursor PAP(248-286). J. Phys. Chem. B, 116: 3650-3658.

24. Huang, R., V. Subramanian, J.R. Brender, Y. Abe, A. Naito and A.Ramamoorthy. 2012. NMR Characterization of Monomer and Oligomeric Conformations of Human Calcitonin and its Interaction with EGCG. J. Mol. Biol., 416: 108-120.

23. Brender, J.R., S. Salamekh, and A. Ramamoorthy. 2012. Membrane Disruption and Early Events in the Aggregation of IAPP from a Molecular Prospective. Acc. Chem. Res., 45: 454-462. Invited Review.

22. Salamekh, S., J.R. Brender, S-J Hyung, R.P.R. Nanga, S. Vivekanandan, B.T. Ruotolo and A. Ramamoorthy. 2011. Evidence for the Inhibition of Human IAPP Fiber Formation by Zinc through the Formation of Off-Pathway Oligomers. J. Mol. Biol., 410: 294-306

21. Yoo, S.I., M. Yang, J.R. Brender, K.Sun, S.H. Jeong, S.Vivekanandan, A. Ramamoorthy, and N. A. Kotov. 2011 Inhibition of Amyloid-beta Peptide Fibrillation by Tetrahedral Nanoparticles and its Mechanism. Angew. Chem. Int. Ed., 50: 5110-5115. Cover

20. Vivekanandan, S., J.R Brender. S.Y. Lee, and A. Ramamoorthy. 2011. A Partially Folded Structure of Amyloid-Beta(1-40) in an Aqueous Environment, Biochem. Biophys. Res. Commun., 411: 312-316.

19. Nanga, R.P.R., J.R. Brender, S. Vivekanandan, and A. Ramamoorthy. 2011. Structure and Membrane Orientation of IAPP in its Natively Amidated Form at Physiological pH in a Membrane Environment Biochim. Biophys Acta-Biomemb., 1808: 2337-2342.

18. Brender, J.R., R.P.R. Nanga, N. Popovych, R.Soong, P.M. Macdonald, and A. Ramamoorthy. 2011. The Amyloidogenic SEVI Precursor, PAP248-286, is Highly Unfolded in Solution despite an Underlying Helical Tendency. Biochim. Biophys Acta-Biomemb., 1808: 1161-1169.

17. Brender, J.R., E.L. Lee, K. Hartman, P. T. Wong, A. Ramamoorthy, D.G. Steel, and A. Gafni. 2010. Biphasic Effects of Insulin on Islet Amyloid Polypeptide Membrane Disruption. Biophys. J., 100: 685-692.

16. Zimmerman, L.B., B.V. Worley, J. R. Brender, K.D. Lee, A. Ramamoorthy, and M.E. Meyerhoff. 2011. Absorbance Based Assay for Membrane Disruption by Peptides Using Pyrroloquinoline Quinone Loaded Liposomes. Anal. Biochem., 411: 194-199.

15. Brender, J. R., K. Hartman, R. P. Nanga, N. Popovych, R. de la Salud Bea, S. Vivekanandan, E. N. Marsh, and A. Ramamoorthy. 2010. Role of Zinc in Human Islet Amyloid Polypeptide Aggregation. J. Am. Chem. Soc., 132: 8973-8983.

14. Smith, P. E., J. R. Brender, U. H. Durr, J. Xu, D. G. Mullen, M. M. Banaszak Holl, and A. Ramamoorthy. 2010. Solid-State NMR Reveals the Hydrophobic-Core Location of Poly(Amidoamine) Dendrimers in Biomembranes. J. Am. Chem. Soc., 132: 8087-8097.

13. Soong, R., J. R. Brender, P. M. Macdonald, and A. Ramamoorthy. 2009. Association of Highly Compact Type II Diabetes Related Islet Amyloid Polypeptide Intermediate Species at Physiological Temperature Revealed by Diffusion NMR Spectroscopy. J. Am. Chem. Soc., 131: 7079-7085.

12. Smith, P. E. S., J. R. Brender, and A. Ramamoorthy. 2009. Induction of Negative Curvature as a Mechanism of Cell Toxicity by Amyloidogenic Peptides: The Case of Islet Amyloid Polypeptide. J. Am. Chem. Soc., 131: 4470-4478.

11. Nanga, R. P. R., J. R. Brender, J. D. Xu, K. Hartman, V. Subramanian, and A. Ramamoorthy. 2009. Three-Dimensional Structure and Orientation of Rat Islet Amyloid Polypeptide Protein in a Membrane Environment by Solution NMR Spectroscopy. J. Am. Chem. Soc., 131: 8252-8261.

10. Nanga, R. P. R., J. R. Brender, S. Vivekanandan, N. Popovych, and A. Ramamoorthy. 2009. NMR Structure in a Membrane Environment Reveals Putative Amyloidogenic Regions of the SEVI Precursor Peptide PAP(248-286). J. Am. Chem. Soc., 131: 17972-17979.

9. Brender, J. R., K. Hartman, L. M. Gottler, M. E. Cavitt, D. W. Youngstrom, and A. Ramamoorthy. 2009. Helical Conformation of the SEVI Precursor Peptide PAP(248-286), a Dramatic Enhancer of HIV Infectivity, Promotes Lipid Aggregation and Fusion. Biophys. J., 97: 2474-2483.

8. Barry, J., M. Fritz, J. R. Brender, P. E. S. Smith, D. K. Lee, and A. Ramamoorthy. 2009. Determining the Effects of Lipophilic Drugs on Membrane Structure by Solid-State NMR Spectroscopy: The Case of the Antioxidant Curcumin. J. Am. Chem. Soc., 131: 4490-4498.

7. Nanga, R. P. R., J. R. Brender, J. D. Xu, G. Veglia, and A. Ramamoorthy. 2008. Structures of Rat and Human Islet Amyloid Polypeptide IAPP(1-19) in Micelles by NMR Spectroscopy. Biochemistry, 47: 12689-12697.

6. Brender, J.R., E. L. Lee, M. A. Cavitt, A. Gafni, D. G. Steel, and A. Ramamoorthy. 2008. Amyloid Fiber Formation and Membrane Disruption are Separate Processes Localized in Two Distinct Regions of IAPP, the Type-2-Diabetes-Related Peptide. J. Am. Chem. Soc., 130: 6424-6429.

5. Brender, J. R., K. Hartman, K. R. Reid, R. T. Kennedy, and A. Ramamoorthy. 2008. A Single Mutation in the Nonamyloidogenic Region of Islet Amyloid Polypeptide Greatly Reduces Toxicity. Biochemistry, 47: 12680-12688.

4. Brender, J. R., U. H. N. Durr, D. Heyl, M. B. Budarapu, and A. Ramamoorthy. 2007. Membrane Fragmentation by an Amyloidogenic Fragment of Human Islet Amyloid Polypeptide Detected by Solid-State NMR Spectroscopy of Membrane Nanotubes. Biochim. Biophys Acta-Biomemb., 1768: 2026-2029.

3. Brender, J. R., J. Dertouzos, D. P. Ballou, V. Massey, B. A. Palfey, B. Entsch, D. G. Steel, and A. Gafni. 2005. Conformational Dynamics of the Isoalloxazine in Substrate-Free p-Hydroxybenzoate Hydroxylase: Single-Molecule Studies. J. Am. Chem. Soc. 127: 18171-18178.

2. Wang, L. C., Y. X. Pang, T. Holder, J. R. Brender, , Kurochkin, A. V. and E. R. P. Zuiderweg. 2001. Functional Dynamics in the Active Site of the Ribonuclease Binase. Proc. Natl. Acad. Sci. U.S.A., 98: 7684-7689.

1. Brender, J. R., D. M. Taylor, and A. Ramamoorthy. 2001. Orientation of Amide-Nitrogen-15 Chemical Shift Tensors in Peptides: A Quantum Chemical Study. J. Am. Chem. Soc., 123: 914-922.