- Undergraduate Education
- B.S. National University of Mexico (1987)
- Graduate Education
- M.S. National University of Mexico (1989)
- Ph.D. London School of Hygiene and Tropical Medicine (1993)
- Postdoc. National Institute of Medical Research, UK (1994)
- Postdoc. Johns Hopkins School of Medicine (1995-2001)
- Joined Texas A&M in 2001
Areas of Research:
RNA Biology in trypanosomes mitochondria
We combine approaches in molecular genetics, structural biology, biochemistry, proteomics, and bioinformatics to study the amazing RNA biology of trypanosome parasites. One research line is on an RNA editing process by uridine insertion and deletion that creates amino acid coding triplets in most mRNAs. Yet a single error in the U-changes yields a frame-shift. Trypanosomes split from other eukaryotic lineages over 100 Ma, yet this editing has analogies with RNAi, CRISPR/Cas9, mRNA splicing and other systems directed by small non-coding RNAs (ncRNAs).
RNA editing is catalyzed by holo-editosomes that include several RNP subcomplexes with over 40 proteins, mRNAs, and hundreds of non-coding guide RNAs (gRNAs). We focus on the regulatory mechanisms of holo-editosome assembly and function. For example, we identified the first catalytic accessory mRNP (termed REH2C), which includes mRNA, the RNA Editing Helicase 2 (REH2) and an intriguing 8-zinc finger termed REH2-Associated Factor 1 (H2F1). We now reconstituted a catalytically active REH2C complex using full-length recombinant proteins. We also have a long tradition using in vitro assays with synthetic RNAs and purified editing components. Multiple collaborations add expertise in protein and RNA structure, homology modeling, deep sequencing, and proteomics to our studies of this vital process in major human parasites.
Development of lead compounds against trypanosomes
A recent new line of investigation in our lab is an exciting collaboration with Tom Meek’s lab that proposes to develop lead drugs with selective inhibitory activity against major potential targets in T. brucei and T. cruzi, the causative agents of important human diseases: African Sleeping Sickness and American Chagas Disease, respectively. Currently, we are testing drugs developed in the Meek lab against N-ribosyl transferases, cruzain, and TbCat B. Our studies also involve molecular analysis of the relevant genes in trypanosomes.
Aphasizheva, I, Alfonzo, J, Carnes, J, Cestari, I, Cruz-Reyes, J, Göringer, HU et al.. Lexis and Grammar of Mitochondrial RNA Processing in Trypanosomes. Trends Parasitol. 2020;36 (4):337-355.
Chenna, BC, Li, L, Mellott, DM, Zhai, X, Siqueira-Neto, JL, Calvet Alvarez, C et al.. Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity. J. Med. Chem. 2020;63 (6):3298-3316.
Kumar, V, Doharey, PK, Gulati, S, Meehan, J, Martinez, MG, Hughes, K et al.. Protein features for assembly of the RNA editing helicase 2 subcomplex (REH2C) in Trypanosome holo-editosomes. PLoS ONE. 2019;14 (4):e0211525.
Cruz-Reyes, J, Mooers, BHM, Doharey, PK, Meehan, J, Gulati, S. Dynamic RNA holo-editosomes with subcomplex variants: Insights into the control of trypanosome editing. Wiley Interdiscip Rev RNA. 2018;9 (6):e1502.
Cruz-Reyes, J, Mooers, BH, Abu-Adas, Z, Kumar, V, Gulati, S. DEAH-RHA helicase•Znf cofactor systems in kinetoplastid RNA editing and evolutionarily distant RNA processes. RNA Dis. ;3 (2):.
Kumar, V, Madina, BR, Gulati, S, Vashisht, AA, Kanyumbu, C, Pieters, B et al.. REH2C Helicase and GRBC Subcomplexes May Base Pair through mRNA and Small Guide RNA in Kinetoplastid Editosomes. J. Biol. Chem. 2016;291 (11):5753-64.
Madina, BR, Kumar, V, Mooers, BH, Cruz-Reyes, J. Native Variants of the MRB1 Complex Exhibit Specialized Functions in Kinetoplastid RNA Editing. PLoS ONE. 2015;10 (4):e0123441.
Madina, BR, Kumar, V, Metz, R, Mooers, BH, Bundschuh, R, Cruz-Reyes, J et al.. Native mitochondrial RNA-binding complexes in kinetoplastid RNA editing differ in guide RNA composition. RNA. 2014;20 (7):1142-52.
Madina, BR, Kuppan, G, Vashisht, AA, Liang, YH, Downey, KM, Wohlschlegel, JA et al.. Guide RNA biogenesis involves a novel RNase III family endoribonuclease in Trypanosoma brucei. RNA. 2011;17 (10):1821-30.
Reifur, L, Yu, LE, Cruz-Reyes, J, Vanhartesvelt, M, Koslowsky, DJ. The impact of mRNA structure on guide RNA targeting in kinetoplastid RNA editing. PLoS ONE. 2010;5 (8):e12235.