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 40 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
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
Mitigating RNA Toxicity in Myotonic Dystrophy using Small Molecules
Reddy K#, Jenquin J, Cleary JD & Berglund JA# (#Co-corresponding authors)
International Journal of Molecular Sciences · August 17, 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
Principal Investigator
Kaalak Reddy
Research Faculty; Adjunct Assistant Professor of Biological Sciences
Life Sciences 02099
members
Current Lab Members
Former Lab Members
Thomas Jambunathan
Cornell University BS 2018 - 2022, RNA Institute Undergraduate Summer Research Program
Reddy Lab News
Berglund and Reddy Labs awarded NIH R01 Grant from National Institute of Neurological Disorders and Stroke
Berglund and Reddy Labs awarded NIH R01 Grant from National Institute of Neurological Disorders and Stroke to study new compounds being developed by the Berglund Lab for myotonic dystrophy
Reddy Lab publishes new research describing the effects of inosine misincorporation into RNA, associated with ITPase deficiency, on translation
Inosine misincorporation into RNA is also detected in Itpa-null mouse embryonic heart tissue as an increase in relative variants compared with the wild type using Illumina RNA sequencing. By generating CRISPR/Cas9 rat H9c2 Itpa-null cardiomyoblast cells, we validate a translation defect in cells that accumulate inosine within endogenous RNA.
Reddy Lab Supports International Myotonic Dystrophy Awareness Day September 15th
Members of the Reddy Lab and DM researchers from The RNA Institute pose for a group photo in support of International Myotonic Dystrophy Awareness Day on September 15th.
Congrats to Jacob!
Jacob Schroader from the Reddy lab has been granted an RNA Fellowship and joins the 7th cohort of RNA Fellows.
UAlbany Spearheads Pooled Saliva Testing on Students and Staff
Reddy Lab joins team for UAlbany COVID-19 pooled surveillance testing program. Andrew Berglund, director of the University’s RNA institute, says they teamed up with UAlbany’s School of Public Health to provide pooled surveillance testing to all their students and staff.
“In this building we have biologists, chemists; by bringing together all different researchers, it tends to move the science forward faster,” Berglund said.