Publications | Lab Members
Overview of Reddy Lab
We are investigating how RNA dysfunction can cause neuromuscular disease and leveraging this knowledge to develop new therapeutic strategies. Our research is focused on myotonic dystrophy and on human ITPase enzyme deficiency using a combination of biochemical, cellular and genomic approaches.
Research
Ongoing Projects
Project 1
Microsatellite expansion disorders are a group of more than 60 neurological, neuromuscular and neurodegenerative diseases caused by expansions of simple DNA tandem repeat sequences (microsatellites). This group includes myotonic dystrophy types 1 and 2, caused by a CTG and CCTG repeat expansion respectively, C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia, caused by a GGGGCC repeat expansion and Huntington disease caused by a CAG expansion. These repeats form toxic RNA molecules that lead to many detrimental downstream cellular consequences. We aim to understand how these toxic RNA molecules are regulated within the cell and to leverage this knowledge to design therapeutic strategies for the associated disorders.
Project 2
Human ITPase enzyme deficiency can result in severe developmental anomalies and is typically fatal in childhood with dilated cardiomyopathy as a major cause of death. The ITPase enzyme prevents accumulation of inosine and deoxyinosine triphosphate within NTP and dNTP pools. In the absence of ITPase, inosine accumulation can result in misincorporation into RNA and DNA. While the biochemical activity of ITPase is well understood, the molecular and cellular basis of pathogenesis resulting from ITPase dysfunction is unknown. We are studying the molecular and cellular consequences of ITPase dysfunction during development to better understand this rare genetic condition and to better understand gene networks that are active during normal healthy development that may be disrupted due to inosine misincorporation.
Reddy Lab Publications
Selected Publications
Expression levels of core spliceosomal proteins modulate the MBNL-mediated spliceopathy in DM1
Jiss M Louis, Jesus A Frias, Jacob H Schroader, Lindsey A Jones, Emily E Davey, Claudia D Lennon, Jacob Chacko, John D Cleary, J Andrew Berglund, Kaalak Reddy
Human Molecular Genetics, 2024, ddae125
The unusual structural properties and potential biological relevance of switchback DNA
Bharath Raj Madhanagopal, Hannah Talbot, Arlin Rodriguez, Jiss Maria Louis, Hana Zeghal, Sweta Vangaveti, Kaalak Reddy, Arun Richard Chandrasekaran
Nature Communications, 2024, s41467-024-50348-3
Jacob H Schroader, Mark T Handley, Kaalak Reddy
WIREs RNA, 2023, wrna.1790
Disease-associated inosine misincorporation into RNA hinders translation
Jacob H Schroader, Lindsey A Jones, Ryan Meng, Hannah K Shorrock, Jared I Richardson, Sharon M Shaughnessy, Qishan Lin, Thomas J Begley, J Andrew Berglund, Gabriele Fuchs, Mark T Handley, Kaalak Reddy
Nucleic Acids Research, 2022, gkac709
CCG•CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity
Barbara A Perez, Hannah K Shorrock, Monica Banez-Coronel, Tao Zu, Lisa EL Romano, Lauren A Laboissonniere, Tammy Reid, Yoshio Ikeda, Kaalak Reddy, Christopher M Gomez, Thomas Bird, Tetsuo Ashizawa, Lawrence J Schut, Alfredo Brusco, J Andrew Berglund, Lis F Hasholt, Jorgen E Nielsen, SH Subramony, Laura PW Ranum
EMBO Mol Med (2021)e14095
Reddy K, Jenquin J, McConnell O, Cleary JD, Richardson JI, Pinto BS, Haerle MC, Delgado E, Planco L, Nakamori M, Wang ET and Berglund JA
Proceedings of the National Academy of Sciences of the United States of America · October 15, 2019
ITPase deficiency causes a Martsolf-like syndrome with a lethal infantile dilated cardiomyopathy
Handley MT*, Reddy K*, Wills J, Rosser E, Kamath A, Halachev M , Falkous G, Williams D, Cox P, Meynert A, Raymond E, Morrison H, Brown S, Allan E, Aligianis I, Jackson AP, Ramsahoye BH, von Kriegsheim A, Taylor RW, Finch AJ and FitzPatrick DR (*Co-first authors)
PLoS Genetics · March 11, 2019
Ribonuclease H2 mutations activate the cGAS-STING nucleic-acid sensing pathway
Mackenzie KJ, Carroll P, Lettice L, Tarnauskaite Z, Reddy K, Dix F, Revuelta A, Abbondati E, Rigby RE, Rabe B, Kilanowski F, Grimes G, Fluteau A, Devenney PS, Hill RE, Reijns MAM and Jackson AP
EMBO Journal · February 22, 2016
TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism
Harley ME, Murina O, Leitch A, Higgs MR, Bicknell LS, Yigit G, Blackford AN, Zlatanou A, Mackenzie K, Reddy K, Halachev M, McGlasson S, Reijns MAM, Fluteau A, Martin C, Sabbioneda S, Elcioglu NH, Altmüller J, Thiele H, Greenhalgh L, Chessa L, Maghnie M, Salim M, Bober MB, Nürnberg P, Jackson SP, Hurles ME, Wollnik B, Stewart GS and Jackson AP
Nature Genetics · November 23, 2015
Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability
Reddy K, Schmidt MH, Geist JM, Thakkar NP, Panigrahi GB, Wang YH and Pearson CE
Nucleic Acids Research · August 21, 2014
Reddy K, Zamiri B, Stanley SYR, Macgregor, RB and Pearson CE
The Journal of Biological Chemistry · April 05, 2013
Current Lab Members
Former Lab Members
Thomas Jambunathan
Cornell University BS 2018 - 2022, RNA Institute Undergraduate Summer Research Program
The RNA Institute
Reddy Lab News
Jacob Schroader presents his work at the 2024 New York RNA Symposium in the Finger Lakes
Jacob was selected to present his work entitled "Inosine misincorporation: a potential driver of cellular dysfunction in ITPase deficiency".
Berglund and Reddy Labs awarded $3M by Department of Defense
UAlbany's Berglund and Reddy Labs were awarded $3M in federal funding over 4 years by the Department of Defense to study new therapeutic approaches and genetic modifiers for myotonic dystrophy.
Congratulations, Jacob!
Congrats and best of luck to our former undergraduate research student Jacob Chacko who graduated from UAlbany and will be starting Med School at Upstate in July!
Jiss presents at the International Myotonic Dystrophy Consortium 14 Meeting in Nijmegen, Netherlands
Dr. Jiss Maria Louis gave a talk titled ‘Expression levels of core spliceosomal proteins modulate the MBNL-mediated spliceopathy in myotonic dystrophy.’
Kaalak Presents at Myotonic Dystrophy Foundation Annual Conference
Kaalak presented "Toxic RNA Selective Screening to Identify Drugs, Targets & Genetic Modifiers for Myotonic Dystrophy" at the Myotonic Dystrophy Foundation Annual Conference held in Washington DC in September 2023. A recording of Kaalak's presentation can be found on youtube.