Professor of Medicine Division of Infectious Diseases M.D., 1980, Northwestern University;   Postdoctoral Fellow, 1985­1989, Case Western Reserve University.

Email: kron@msu.edu Phone: (517) 353-3747  Lab: 353-3747 Fax: 353-1922  Home Department: Medicine, CHM

I. Aminoacyl­tRNA synthetase (AARS) are the fundamental group of cytoplasmic and mitochrondrial biosysnthetic enzymes which function in the highly specific reaction to aminoacylate or "charge" tRNA with the cognate aminoacid. Each enzymes binds three substrates: ATP, tRNA, and amino acid, along with an adenylate intermediate. For each amino acid and tRNA, highly specific enzymes have evolved to maintain the fidelity of protein synthesis at this very basic level. Despite highly conserved function within and between species, AARS display little overall homology at the primary or secondary structural levels. However, all AARS can be grouped into two classes based on catalytic domain topologies. Devergence of structure has been hypothesized to account for both the specificity of each enzyme viz a viz diversity of tRNA structures, as well as to accommodate several additional/alternate functions for these enzymes.

My research focuses on examining the structure function relationships between cloned class II AARS derived from nematode parasites. The ability to mount neutralizing antibody responses to many eukaryotic AARS involved in immunological disease is genetically linked to speicific class II HLA markers and immunoglobulin allotypes. Understanding AARS structure and function has wide practical application in the fields of rational drug design and understanding the pathogenesis of some autoimmune diseases.

II. Immunoglobulin (Ig) allotypes are hereditary antigenic determinants on Ig polypeptide chains. They are polymorphic within species and can be used as genetic markers. These determinants are inherited as autosomal codominant genes according to Mendelian laws. In our investigations, we focus on the Gm and Km allotypes, the antigenic determinants of IgG heavy chains and the k­type light chains, respectively. Gm allotypes are encoded by three very closely linked cistrons on chromosome 14 and they are localized on the constant region of g1, g2 and g3 heavy chains.

Gm and Km allotypes have been shown by several laboratories to be associated with susceptibility and/or resistance to several diseases, including several bacterial or viral infectious diseases. Moreover, immune responsiveness to numerous antigens appears to be influenced by Gm and Km genes. The role of these genes in determining the clinical­immunological responses to human filarial infections has never been explored, yet the spectrum of clinical disease seen with these parasitic diseases is clearly associated with hyper­ or hyporesponsive states to antifilarial antibodies.

SELECTED PUBLICATIONS:
M. Kron, et al. Hyperimmunoglobulinemia E in the absences of filariasis: The Huaorani of Ecuador. (accepted, Asthma Allergy Proceedings.)

M Kron , E. Walker, B. Ramirez, L. Hernandez (2000). Filariasis in the Philippines. Parasitology Today . Vol 16, no 8, 229-232.

M. Kron, B. Ramirez, J. Pandey (1999). Immunogloblin allotypes in the Bicolano of Sorsogon Province, Philippines: Implications of phenotypes for filariasis. Experimental and Clinical Immunogenetics 16:65-71

M. Hirikata, M Kron et al. (1999). Characterization of anti-KS: autoantibody against human cytoplasmic AsnRS. J. Immunology Feb 15;162(4):2315-20.

Other Publications
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