The cells in the human body are constantly trying to overcome damage to their DNA that results from both exogenous (tobacco smoke, alcohol) and endogenous sources (Reactive aldehydes, ROS) of stress, to ensure normal cellular function. Dysregulation of critical cellular processes, such as DNA replication, repair or transcription, can lead to chromosomal aberrations that lead to malignancies and other debilitating diseases. The overarching goal of our research is to identify markers of replication stress that can help stratify patients in terms of prognosis and response to treatment measures.
Research in our lab largely focuses on elucidating the molecular mechanisms that underlie the pathogenesis of cancer-predisposition syndromes and hematological malignancies. In particular, we are exploring the contribution of defective replication, transcription and repair to genomic instability in disorders like Fanconi anemia and Adult T-cell leukemia/lymphoma. In addition to our studies on determining the molecular basis of cancer-predisposition, we are also interested in understanding the primary mechanisms underlying hematopoietic stem cell exhaustion/attrition and bone marrow failure in Fanconi anemia using a human stem cell model for FA.
All of our strategies and approaches are aimed at identifying key markers (proteins, secondary structures, genomic hotspots, chromatin conformation changes) that could directly help in tailoring therapeutic regimes for cancer patients. In addition, since our research investigates changes at the earliest stages of the disease, we have the power to identify changes (in molecular mechanisms) that are causal in disease manifestation, while eliminating confounding consequential changes that occur downstream
We study changes in DNA replication at the single molecule level using fluorescent microscopy, we use genomics to study secondary structure formation and collisions between DNA replication and transcription machinery by a specialized ChIP-seq analysis, and we study changes in topologically associated domains that are strongly implicated in transcriptional changes that destabilize tumor suppressor genes or activate proto-oncogenes.
Single molecule analysis of replicating DNA (SMARD)
Cells are sequentially pulsed with two halogenated nucleosides to label replicating DNA. Pulsed cells are lysed in agarose plugs and genomic DNA digested with a restriction endonuclease to produce 100 – 600 kb segments. The DNA is separated by pulsed field gel electrophoresis and the target segment identified by Southern blotting. A gel slice containing the target segment is excised and melted and the DNA in solution is stretched on silanized slides. Halogenated nucleosides are then detected by immunostaining. Biotinylated FISH probes identify the molecules of interest and are used to align the images of molecules to produce a composite replication profile.
Sourabh Prakash Mudakannaver
The Madireddy lab is officially open!!!
The National Heart, Lung and Blood Institute has funded the Madireddy Lab’s R00 application
A warm welcome to Sourabh Prakash Mudakannaver and Priyanka Tiwari, the newest members of our lab.
The lab is now funded by the American Cancer Society Pilot Grant.
A very warm welcome to Angelica Barreto, a new graduate student who is doing her PhD rotation in our lab.
Welcome to Anam Shaikh, our newest undergraduate intern
The Madireddy Lab is growing, we have now recruited our very first Postdoctoral Fellow. A warm welcome to Dr. Angelo Mandarino.
NIH - National heart, lung and blood institute 2017-2022
American Cancer Society 2019
Rutgers Cancer Institute of New Jersey
We are always looking for scientists who are passionate about research. If you are interested in joining the Madireddy Lab, please send us an application with your cover letter (describing your interests), your CV, and contact information for 2-3 reference providers.
We are looking for a lab manager/lab technician for the lab. The official posting for this job is now available online. You are also welcome to contact us directly using the contact form.
We invite enthusiastic graduate students from the Molecular Biosciences Graduate program for a lab rotation. Refer to the following website for faculty information:
Rutgers Cancer Institute of New Jersey
195, Little Albany Street
New Brunswick, NJ 08901