Reddy Lab

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
 

Reddy-project-1

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.

Reddy-project-2

 

 

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

 

A CTG-repeat-selective chemical screen identifies microtubule inhibitors as selective modulators of toxic CUG RNA levels

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

 

The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures

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
Andrea Aguanno
Undergraduate Research Student
Jacob Chacko
Undergraduate Research Student (BS 2024)
Jiss Louis
Postdoctoral Fellow-joint appointment with Berglund lab and Reddy lab
Jacob Schroader
PhD Student Co-supervised by Dr. Andrew Berglund
Former Lab Members
Ty Hamel
Reddy Lab Undergraduate (2022)
BSc 2023
Thomas Jambunathan
Cornell University BS 2018 - 2022, RNA Institute Undergraduate Summer Research Program
Lindsey Jones
Research Technician (2020-2022)
Marufa Kasham
Reddy Lab Undergraduate (2022)
BS/BA 2022
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