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Welcome to the Misra Lab

Mentoring

To me, maintaining a healthy and cordial environment for every lab member is a top priority. My lab maintains a culture of support, awareness, and positive communication. Research involves a lot of failure, which can be be stressful, and is especially so for those with additional challenges. In my lab, I promote a culture of reasonable work-life balance, to ensure that lab members with diverse external pressures can flourish. I  ensure that all members feel comfortable to engage in scientific exchange, irrespective of their background and experience and realize that their contributions are highly valued. I encourage every lab members to present their work to the lab group and to participate in external meetings.

 

I expect all lab members to help each other, keep the lab organized, and generally be responsible citizens. There are tedious tasks that need to be done to keep the lab running, and we will all share these responsibilities. It is not important how many hours you spend physically in the lab.  Instead I will monitor your progress you make on your project. Experiments fail most of the time. Learning to troubleshoot and overcome setbacks is key to progress and maintaining your happiness. Please always think through the steps of an experiment yourself. I may not always have all the correct answers, and could at times, give you incorrect information. However, I will try my best to steer you in the right direction. I expect dedication and hard work, but in return you will receive my fierce support for you and your career.

 

I want you to feel comfortable to communicate with me about any issues that arise during your time in my lab, and I will assist you in whatever way is most helpful to you. Please let me know if there is anything you would like to change about the way the lab is run, and I will take your input into consideration.

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Research

Regulation of growth during development and cancer

Have you ever wondered why our hands never grow to touch our feet?  For that matter, every organ in the body has a very specific size and form (patterning) for optimal function. In some cases, even a slight change in the size and shape can lead to serious health condition. For example, a slight defect in heart can often be lethal. Then the question is: how do the organs know when to stop growing? More importantly, you may be thinking why should we care about this question. It turns out that every cell in the body has an intrinsic mechanism to control growth, and when these mechanisms fail, they grow in an uncontrolled manner and give rise to cancer.  

We seek to understand how tissue growth is precisely regulated during embryonic development and how dysregulation of this process result in devastating diseases such as cancer. We use the fruit fly, Drosophila melanogaster as a model organism to study how the Hippo signaling pathway and the protocadherins, Dachsous and Fat play an important role in tissue growth and patterning regulation. We are also striving to develop novel chemical inhibitors of Hippo signaling, which is deregulated in most human cancers. 

Regulation of growth and morphogenesis during development

Left: Schematic of Hippo signaling pathway. Right: Overgrowth of Hippo mutant clones in Drosophila and Mst1/2 mutant mouse liver.

 

Proper size and shape is required for optimal functioning of organs. In multicellular organisms, different tissues develop to a characteristic final size and shape, and maintain an optimal proportion to the body. Misregulation of growth and morphogenesis during development results in structural birth defects that last into adulthood and often lead to organ malfunction. Thus precise coordination of growth and morphogenesis is a fundamental aspect of development that is essential for normal organ function and body organization. The evolutionarily conserved Hippo signaling pathway plays a central role in organ size control and is associated with many cancers. The protocadherins, Dachsous (Ds) and Fat are conserved upstream regulators of Hippo signaling that play a key role in coordinating growth and morphogenesis. Ds and Fat restrict growth by activating Hippo signaling and influence morphogenesis by regulating planar cell polarity and oriented cell divisions. Consistently, mutations affecting this pathway result in a number of diseases affecting organ shape or size, such as Hennekam syndrome and Van Maldergem syndrome. However, the molecular mechanisms by which Fat signaling regulates growth and morphogenesis are not well understood. I have identified Vamana and Early girl, two novel regulators of this signaling pathway. Additionally, my work has led to intriguing findings that suggest that vesicular trafficking plays a crucial role in regulating this pathway, an aspect that is very little explored. Our lab employs an  interdisciplinary approach using Drosophila genetics, cell biology and biochemistry to study the vesicular trafficking mechanisms that organize this signaling pathway and  to identify novel regulators of this pathway.

Development of novel inhibitors of YAP activity for cancer therapy

The Hippo signaling pathway plays a central role in growth regulation from fruit flies to humans. This pathway is misregulated in most human cancers, where the terminal effector of the pathway, YAP/TAZ (blue/green) binds to the TEAD1-4 (grey) transcription factors and constitutively induces the transcription of a number of genes that promote carcinogenesis. In collaboration with computational and medicinal chemists we are developing novel inhibitors of YAP activity with the aim to develop therapeutics for YAP-driven cancers.

Home: Research

Publications

Gridnev, A., Maity S. Misra JR. Structure-based discovery of a small-molecule inhibitor of TEAD palmitoylation with anticancer activity.  Frontiers in Oncology. 2:1021823. doi: 10.3389/fonc.2022.1021823.

Artem Gridnev, Misra JR. Emerging mechanisms of growth and patterning regulation by Dachsous and Fat protocadherins. Frontiers in Cell and Developmental Biology. 2022. 10:842593. doi: 10.3389/fcell.2022.842593

Subhajit Maity, Artem Gridnev, Misra JR. Assays used for discovering small molecule inhibitors of YAP activity in cancers. Cancers (Basel). 2022. 14(4):1029. doi: 10.3390/cancers14041029.

Misra JR, Irvine KD. Early girl is a novel component of the Fat signaling pathway. PLoS Genet. 2019 Jan 30;15(1):e1007955. doi: 10.1371/journal.pgen.1007955.

Misra JR, Irvine KD. The Hippo Signaling Network and Its Biological Functions. Annu Rev Genet. 2018 Nov 23;52:65-87. doi: 10.1146/annurev-genet-120417-031621.

Misra JR, Irvine KD. Vamana Couples Fat Signaling to the Hippo Pathway. Dev Cell. 2016 Oct 24;39(2):254-266. doi: 10.1016/j.devcel.2016.09.017.

Misra JR, Lam G, Thummel CS. Constitutive activation of the Nrf2/Keap1 pathway in insecticide-resistant strains of Drosophila. Insect Biochem Mol Biol. 2013 Dec;43(12):1116-24. doi: 10.1016/j.ibmb.2013.09.005.

Misra JR, Horner MA, Lam G, Thummel CS. Transcriptional regulation of xenobiotic detoxification in Drosophila. Genes Dev. 2011 Sep 1;25(17):1796-806. doi: 10.1101/gad.17280911.

Kumar D, Kumar A, Misra JR, Chugh J, Sharma S, Hosur RV. 1H, 15N, 13C resonance assignment of folded and 8 M urea-denatured state of SUMO from Drosophila melanogaster. Biomol NMR Assign. 2008 Jun;2(1):13-5. doi: 10.1007/s12104-007-9072-6.

Kumar D, Misra JR, Kumar A, Chugh J, Sharma S, Hosur RV. NMR-derived solution structure of SUMO from Drosophila melanogaster (dSmt3). Proteins. 2009 Jun;75(4):1046-50. doi: 10.1002/prot.22389.

Chugh J, Sharma S, Kumar D, Misra JR, Hosur RV. Effect of a single point mutation on the stability, residual structure and dynamics in the denatured state of GED: relevance to self-assembly. Biophys Chem. 2008 Sep;137(1):13-8. doi: 10.1016/j.bpc.2008.06.005.

Members

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Jyoti Misra

Principal Investigator

News

November 2022
Congratulations to Artem Gridnev for his first author paper getting accepted in Frontiers in Oncology!

October 2022
Netanya joins as Research Technician. Welcome!


Sept 2022
Welcome to rotation student Preethi, and Masters students Hrishikesh and Siddhi.


May 2022
Congratulations to our undergraduate Pragya Rawat for getting into the Boston University Graduate School! We wish you  the best!

The Misra lab received a SPIRe seed grant from the UTD Office of Research and Innovation!

Congratulations to the Misra Lab undergraduates for graduating!

April 2022
Congratulations to Subhajit Maity for getting a UTD Graduate Research and Cancer Education (GRACE) Fellowship !

February 2022
Congratulations to Charukesi Sivakumar for getting into University of Michigan Graduate School!
Welcome to rotation student Ujjaini Basu and undergraduate Dalia Salam-Ahmed

November 2021
We were awarded a Google Cloud Research Credit for computational drug discovery.


Sept 2021
The Misra lab was awarded a R35 MIRA grant from NIGMS

Welcome to rotation students Subhajit Maity and Grant Shryock!

We were selected for an AIMs award from Atomwise.

May 2021
Congratulations to Tharani for completing her masters and joining her new role in industry.

Fall 2020
Congratulations to Pragya and Charu for getting selected for the Green Fellowship.

Jan 2020
Artem Gridnev joins as Research Technician! 

Sept 2019
Misra lab opens door at UTD! 

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Gone but not forgotten



Samuel Koshy, Thien Bui, Pranayi pala, Pragya Rawat
​Charukesi Sivakumar




 

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Resources

Stay in the Know

The tiny fruit fly, Drosophila melanogaster that you see around apples and bananas has been a favorite of scientists for more than a century and has led to some of the groundbreaking discoveries that has resulted in 5 Nobel prizes in Physiology and Medicine. If you are curious why this tiny creature is the "Queen of Genetics"  you can find out more from the following links.

Join Our Lab

Postdocs

We are looking for highly motivated postdocs to join our group. Interested individuals should contact with CV, Cover Letter and contact information for three references.

Graduate Students

We are looking for highly motivated hard working graduate students to join our lab. Interested candidates should contact for rotations along with their CV.

Undergraduate Researchers

We are looking for motivated undergraduates willing to spend at least 12 hours a week in the lab.

Lab Technician

We are currently looking to hire a research technician, who have had a strong interest and experience in biochemistry, molecular biology and genetics.

Contact Us

University of Texas at Dallas, Richardson, TX, 75080, USA

jyoti.misra@ utdallas.edu

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