B.S. (University of Belgrade, 1994)
M.S. (University of Belgrade, 1996)
Ph.D. (Iowa State University, 2001)
Post-Doctoral Work: Department of Physiology, Wayne State University School of Medicine(2002-2006)
In cells there are hundreds of macromolecular assemblies ranging in size of few to over hundred million of
Daltons such as the nuclear pore complex. Despite progress in structural genomics and modern instrumentation,
high resolution structural information is available for only a small fraction of these assembles known to
play critical roles in signal transduction, genetic, and metabolic networks. Even fewer molecular structures
are available for large macromolecular complexes (<100 KD) in which the atomic details of protein-protein,
protein-nucleic acid or protein-lipid interactions have been elucidated. To gain new insights into the structure,
organization and dynamics of these large macromolecular assemblies, my laboratory adopts nano-approach that
includes high-resolution optical, force and spectral imaging, X-ray crystallography and CD/Raman/MS spectroscopy.
By using ß-cell as a model system and with help of a new generation of imaging tools, we seek to elucidate general
principles underlying the self-organization of complex dynamic structures inside cells. Delineating the 3-D
structure and molecular architecture of these super assemblies is essential to mechanistically understand its role
in mediating fundamental biological processes and diseases.
Type II Diabetes mellitus (T2DM) is a complex and heterogeneous metabolic disease that has reached epidemic
proportions. The onset of T2DM is characterized by two determining factors: the insufficient ability to
secrete insulin and/or the resistance to its biological action. The ability to store insulin and release
it in a regulated manner in response to a complex array of physiological signals is the major feature of
pancreatic islet ß-cells. Understanding the mechanism that regulates insulin secretion may allow the
development of novel drug therapies with possibility to adjust secretory deficiencies. Our research goal
is to elucidate more precisely the structure and organization of cellular machinery that regulates insulin
release in ß-cell and to find the cause for islet amyloid fibril formation. These studies should also
reveal underlying general principles of organization of supramolecular complexes and its dynamics in cells.
Aim 1: Unraveling structure and composition of membrane machinery regulating insulin release in ß-cell.
Glucose-induced insulin secretion in ß-cells are biphasic process, consisting of transient and rapid first phase
followed by a sustained second phase. Insulin release is tightly controlled process as only a small fraction of
the ß-cell insulin content is released during secretion. Because T2DM patients have defective insulin secretion,
it is important to understand the cellular mechanism underling biphasic insulin release. We integrate biochemical
and biophysical methods with the high-resolution cell imaging such as atomic force microscopy (AFM) to identify
structure, dynamics and organization of the insulin release machinery located at the ß-cell plasma membrane.
Membrane reorganization and dynamics of insulin release in ß-cell is studied in real time through integrated
optical and force microscopy (confocal / AFM imaging). In biology, the distinct advantage of this scanning probe
microscope over the electron microscope (EM) is its unique ability to directly monitor changes in the conformation
or aggregation state of macromolecules, and to study dynamics aspects of molecular interaction in their physiological
Aim 2: Elucidating the molecular mechanism of aberrant protein (amyloid) formation in the islets of Langerhans.
Genetic, endocrine and environmental factors contribute to the development of diabetes. Late-onset diabetes is typically
associated with amyloid deposits of fibrillar amylin in the pancreatic islets. Islet amyloid polypeptide (IAPP or amylin)
is a 37 aa-residue peptide hormone, a protein co-expressed and secreted with insulin by islet ß-cells. In the late-onset
diabetes, however, it comprises the major fibrillar component of the islet amyloid deposits, a hallmark of T2DM (found
in over 90 % of patients). Diabetes is one of a family of diseases featuring fibrillar amyloid deposits, such as Alzheimerfs
(ß-amyloid), Huntingtonfs disease (huntingtin) and mad-cow (prion) disease. Intervention to control fibril growth and
aggregation has great therapeutic potential, but it requires a rational understanding of the molecular mechanisms governing
fibril assembly and its dynamics in cells. Therefore, by using AFM in our studies, it is possible to reveal conditions in
the cell that enhance or reduce fibril formation. For example, different reagents can be added to the cultured human
ß-cells or islets while fibrils form, and thus their potential as activators or inhibitors of fibril assembly could be
directly (in situ) investigated at the single cell and fibril level. Combination of different methodologies and techniques,
such as intracellular Ca2+ imaging (to study amyloid-induced cell damage), ELISA and/or confocal microscopy (to study the
cell functionality, i.e. assessment of ß-cell to release insulin), photon correlation spectroscopy (to observe formation
of amyloid fibrils and their intermediates), CD and Raman spectroscopy (to study peptide conformational transitions), and
the high-resolution imaging of fibril structures by AFM, will bring us a step closer to the goal of finding the cause for
fibril formation and the etiology of T2DM. The ultimate goal of this part of the study is to control the growth and nature
of amyloid deposits in vivo, which may prove useful for more rational disease management.
Jeremic A, Cho WJ, Jena BP. Cholesterol is critical to the integrity of neuronal porosome / fusion pore.
Ultramicroscopy, 106 (8-9): 674-677 (2006).
Jeremic A, Quinn AS, Cho WJ, Taatjes DJ and Jena BP. Energy-Dependent Disassembly of Self-Assembled SNARE
Complex: Observation at Nanometer Resolution Using Atomic Force Microscopy. Journal of American Chemical
Society,128 (1): 26-27 (2006).
Jeremic A1, Cho WJ1 and Jena BP. Involvement of water channels in synaptic vesicle swelling. Experimental
Biology & Medicine, 230 (9): 674-80 (2005).
Cho WJ, Jeremic A and Jena BP. Size of Supramolecular SNARE complex:
Membrane-Directed Self-Assembly. Journal of American Chemical Society, 127: 10156-7 (2005).
Cho WJ1, Jeremic A1 and Jena BP. Direct Interactions Between SNAP-23 and L-type Ca2+ Channel in Rat
Pancreas Examined by Two Yeast Hybrid System. Journal of Cellular and Molecular Medicine, 9 (2): 380-386 (2005).
Kelly M, Abu-Hamdah R, Jeremic A, Cho SJ, Ilie A and Jena BP. Patch Clamped Single Pancreatic Zymogene Granules:
Direct Measurements of Ion Channel Activities at the Granule Membrane. Pancreatology, 28 (5): 443-449 (2005).
Jeremic A, Cho WJ and Jena BP. Membrane Fusion: What May Transpire at the Atomic Level. Journal of Biological
Physics and Chemistry, 4: 139-142 (2004).
Cho WJ1, Jeremic A1, Rognlien K, Zhvania MZ, Lazrishvili I, Tamar B and Jena BP. Structure, Isolation, Composition
and Reconstitution of the Neuronal Fusion Pore. Cell Biology Int., 28 (10): 699-708 (2004).
Kelly M1, Cho WJ1, Jeremic A1 , Abu-Hamdah R and Jena BP. Vesicle Swelling Regulates Content Expulsion During
Secretion. Cell Biology Int., 28 (10): 709-716 (2004).
Jeremic A, Kelly M, Cho JA, Cho SJ, Hoerber H and Jena BP. Calcium Drives Fusion of SNARE-apposed Bilayers.
Cell Biology Int., 28 (1): 19-31 (2004).
Abu-Hamdah, Cho WJ, Cho SJ, Jeremic A, Kelly M, Elena A and Jena BP. Regulation of the Water Channel Aquaporin 1:
Isolation and Reconstitution of the Regulatory Complex. Cell Biology Int.,28 (1): 7-17 (2004).
Jeremic A1, Kelly M1, Cho SJ, Stromer MH, Jena BP. Reconstituted Fusion Pore. Biophysical Journal, 85(3): 2035-43 (2003).
Jena BP, Cho SJ, Jeremic A, Stromer MH, Abu-Hamdah R. Structure and Composition of the Fusion Pore. Biophysical Journal,
84(2 Pt 1):1337-43 (2003).
Glavaski-Joksimovic A, Jeftinija K, Jeremic A, Anderson LL, Jeftinija S. Mechanism of Action of the Growth Hormone
Secretagogue, L-692,585, on Isolated Porcine Somatotropes. Journal of Endocrinology, 175(3): 625-36 (2002).
Jeremic, A., K. Jeftinija, A. Glavaski and S. Jeftinija. ATP Stimulates Calcium-Dependent Glutamate Release from Cultured
Astrocytes. Journal of Neurochemistry, 77(2):664-75 (2001).
1 - Denotes combined first authorship and equal contribution.
BiSc 106 - Special Topics in Biochemistry. A weekly discussion of current topics in biochemistry, including readings, and in-depth analysis of recent literature.
BiSc 120 - Human Neurobiology. A review emphasizing the cellular and molecular basis for nervous system structure and function.
Dr. Jeremic`s laboratory is open to all undergraduate, graduate and medical students who share common research interests at
the interface of (nano) biology, medicine, physics and chemistry, and want to pursue fundamental questions in the biomedical