Vargheese M. Chennathukuzhi, Ph.D.
Indian Institute of Technology, Madras, India, 1996
Uterine fibroids are the most common tumors of the female reproductive tract, clinically relevant in 20-40% of reproductive aged women, occurring in up to 70% of white and 80% of black women by the age of 50 years. Uterine fibroids account for over 200,000 hysterectomies annually in the United States alone. Currently there is no approved drug for the long-term medical therapy of fibroids. One of our research interests is to understand the biology of an aberrantly expressed G protein-coupled receptor that contributes to the fibroids tumor growth. We utilize genetically modified animal models as well as primary human fibroids cells to study the etiology of uterine leiomyomas. Our goal is to develop small molecule and peptidomimetic drugs for the treatment of uterine fibroids.
My laboratory also studies the biology of a sperm-specific sodium-proton exchanger that regulates intracellular pH and motility of the sperm. In addition we are interested in novel cancer testis antigens and development of targeted cancer therapies.
Selected Recent Publications
1: Varghese BV, Koohestani F, McWilliams M, Colvin A, Gunewardena S, Kinsey WH, Nowak RA, Nothnick WB, Chennathukuzhi VM. The loss of REST in uterine fibroids promotes aberrant GPR10 expression and enables mTOR pathway activation. Proc Natl Acad Sci U S A. 2013 110(6): 2187-92. PMID: 23284171
2: Green fluorescence protein driven by the Na,K-ATPase α4 isoform promoter is expressed only in male germ cells of mouse testis. McDermott JP, Sánchez G, Chennathukuzhi V, Blanco G. J Assist Reprod Genet. 2012;29(12):1313-25. PMID: 23229519
3: Fitzgerald JB, Chennathukuzhi V, Koohestani F, Nowak RA, Christenson LK. Role of microRNA-21 and programmed cell death 4 in the pathogenesis of human uterine leiomyomas. Fertil Steril. 2012 98(3): 726-734. PMID: 22728051
4: Petucci C, Lloyd T, Harris HA, Zhang X, Chennathukuzhi VM, Mekonnen B, Cai Y. Trace LC/MS/MS quantitation of 17beta-estradiol as a biomarker for selective estrogen receptor modulator activity in the rat brain. J Mass Spectrom. 2010 45(1):65-71.
5: Harris HA, Chennathukuzhi VM, Zhang X, Mekonnen B, Jelinsky SA, Schelling SH, Patel VS, Huselton C, Negahban A, Winneker RC. Development of an early biomarker for the ovarian liability of selective estrogen receptor modulators in rats. J Steroid Biochem Mol Biol. 2008, 112: 40-6
6: Cotreau MM, Chennathukuzhi VM, Harris HA, Han L, Dorner AJ, Apseloff G, Varadarajan U, Hatstat E, Zakaria M, Strahs AL, Crabtree JS, Winneker RC, Jelinsky SA. A study of 17b-estradiol-regulated genes in the vagina of postmenopausal women with vaginal atrophy. Maturitas. 2007, 58(4): 366-76.
7: Chengalvala M, Chennathukuzi VM, Johnston D, Stevis P, and Kopf GS. Gene expression profiling and its practice in drug development. Current Genomics 2007, 8, 262-270.
8: Cho YS, Chennathukuzhi VM, Handel MA, Eppig J, Hecht NB. The relative levels of translin-associated factor X (TRAX) and testis brain RNA-binding protein determine their nucleocytoplasmic distribution in male germ cells. J Biol Chem. 2004 279: 31514-23.
9: Bray JD, Chennathukuzhi VM, Hecht NB. KIF2Abeta: A kinesin family member enriched in mouse male germ cells, interacts with translin associated factor-X (TRAX). Mol Reprod Dev. 2004, 69:387-96.
10: Yang S, Cho YS, Chennathukuzhi VM, Underkoffler LA, Loomes K, Hecht NB. Translin-associated factor X is post-transcriptionally regulated by its partner protein TB-RBP, and both are essential for normal cell proliferation. J Biol Chem. 2004 279: 12605-14.
11: Chennathukuzhi V, Morales CR, El-Alfy M, Hecht NB. The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP-responsive element modulator-regulated mRNAs in male germ cells. Proc Natl Acad Sci U S A. 2003 100: 15566-71.
12: Chennathukuzhi V, Stein JM, Abel T, Donlon S, Yang S, Miller JP, Allman DM, Simmons RA, Hecht NB. Mice deficient for testis-brain RNA-binding protein exhibit a coordinate loss of TRAX, reduced fertility, altered gene expression in the brain, and behavioral changes. Mol Cell Biol. 2003 23: 6419-34.
13: Ferrand PE, Fujimoto T, Chennathukuzhi V, Parry S, Macones GA, Sammel M, Kuivaniemi H, Romero R, Strauss JF 3rd. The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM). Mol Hum Reprod. 2002 8:1031-4.
14: Zhang Z, Sapiro R, Kapfhamer D, Bucan M, Bray J, Chennathukuzhi V, McNamara P, Curtis A, Zhang M, Blanchette-Mackie EJ, Strauss JF 3rd. A sperm-associated WD repeat protein orthologous to Chlamydomonas PF20 associates with Spag6, the mammalian orthologue of Chlamydomonas PF16. Mol Cell Biol. 2002 22:7993-8004.
15: Morales CR, Lefrancois S, Chennathukuzhi V, El-Alfy M, Wu X, Yang J, Gerton GL, Hecht NB. A TB-RBP and Ter ATPase complex accompanies specific mRNAs from nuclei through the nuclear pores and into intercellular bridges in mouse male germ cells. Dev Biol. 2002 246:480-94.
16: Pascal JM, Chennathukuzhi VM, Hecht NB, Robertus JD. Mouse testis-brain RNA-binding protein (TB-RBP): expression, purification and crystal X-ray diffraction. Acta Crystallogr D Biol Crystallogr. 2001 57:1692-4.
17: Chennathukuzhi VM, Kurihara Y, Bray JD, Hecht NB. Trax (translin-associated factor X), a primarily cytoplasmic protein, inhibits the binding of TB-RBP (translin) to RNA. J Biol Chem. 2001 276: 13256-63.