May 16, 2020

Megan Reed Student Highlight

Megan is a Ph.D. student in her 5th year in the Biochemistry and Molecular Biology Department. She joined the laboratory of Dr. Robert Eoff for her research studies.

She has a B.S. in Biology with a dual minor in Chemistry and Psychology from Henderson State University.

Research Interest Statement

My project involves elucidating various mechanisms that glioblastoma brain tumors use to tolerate, repair and ultimately survive chemotherapeutic intervention. We are most interested in investigating the alternate functions of the DNA damage tolerance polymerase kappa (hpol k) and how these responses aid in tumor survival. Overexpression of this polymerase has been linked to tumor recurrence and resistance to standard-of-care chemotherapeutics. Understanding the possible ways that hpol k promotes these outcomes could help develop more effective treatments for glioblastoma patients.

Something Notable about Time as a Graduate Student

A fun fact about the Eoff lab is we are all left handed. We have this running joke that a requirement to join the lab is you must be left handed.

In all seriousness though I would say I have really enjoyed being part of the Biochemistry Department. I have built life-long friendships and have received tremendous support not only from my primary advisor but from many of the labs in this department. I like to joke that I am the department’s graduate student as I have pretty much gone to every lab at one time or another asking for experimental advice or to borrow reagents. My graduate school experience wouldn’t have been as successful if it was not for the faculty, postdocs and students that make up the Biochemistry Department.

Career Goals

Once I am finished with my PhD, I plan to pursue post-doctoral research in a lab focused on developing 3D tumor model systems. My long term goal is to conduct research using these model systems to help predict patient drug response, thereby opening up access to personalized chemotherapeutic treatments that are currently unavailable to most cancer patients.

Experiment or Technique You Would Most Like to Do

I really enjoy immunofluorescence microscopy. I don’t think I will ever get tired of taking beautifully colored fluorescent images.

Fun fact

I enjoy spending time with family, friends and hiking with my dog Brain.

Publications

Bostian, A. C., Maddukuri, L. M., Reed, M. R., Savenka, T., Hartman, J. H., Davis, L., Pouncey, D.L., Miller, G.P., and Eoff, R. L. Kynurenine signaling increases DNA polymerase kappa and promotes genomic instability in glioblastoma cells. Chem. Res. Toxicol. 2016, 29(1): 101-8.

Byrd, A. K., Zybailov, B. L., Maddukuri, L., GAO, J., Marecki, J. C., Jaiswal, M., Bell, M. R., Griffin, W.C., Reed, M. R., Chib, S., Mackintosh, S. G., MacNicol, A. M., Baldini, G., Eoff, R. L., and Raney, K. D. Evidence that G-quadruplex DNA accumulates in the cytoplasm and participates in stress granule assembly in response to oxidative stress. J. Biol. Chem. 2016, 24(3): 432-36.

Zafar, M. K., Maddukuri, L., Ketkar, A., Penthala, N.R., Reed, M. R., Eddy, S., Crooks, P. A., and Eoff, R. L. A small-molecule inhibitor of human DNA polymerase h potentiates the effects of cisplatin in tumor cells. Biochemistry. 2018, 57(7): 1262-73.

West, K. L., Kelliher, J. L., Xu, Z., An, L., Reed, M. R., Eoff, R. L., Wang, J., Huen, M. S. Y., and Leung, J. W. C.  LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. Nucleic Acids Res. 2019, 47(12): 6236-6249.

Ketkar, A., Maddukuri, L., Penthala, N. R., Reed, M. R., Zafar, M. K., Crooks, P. A., and Eoff, R. L. Inhibition of human DNA polymerases eta and kappa by indole-derived molecules occurs through distinct mechanisms. ACS Chem Biol. 2019, 14(6): 1337-1351.

Reed, M. R., Maddukuri, L., Ketkar, A., Byrum, S. D., Zafar, M. K., Bostian, A. C. L., Tackett, A. J., and Eoff, R. L. Inhibition of tryptophan-2,3-deoxygenate impairs DNA damage tolerance and repair in glioma cells. (In preparation)

Patents

U.S. Provisional Patent Application No.: 62/792,226

Title: Naphthoyl, napthalenylmethyl, and naphthalenysulfonyl indole aminoguanidine analogs as DNA polymerase kappa inhibitors targeting glioblastoma.

Inventors: Robert L. Eoff, Peter Crooks, Narsimha Penthala, Amit Ketkar, Leena Maddukuri, and Megan Reed

BV Reference No.: 2019-09

Awards

2017: First place overall, for poster presentation at UAMS Student Research Day

2017: First place, Bhuvan award for excellence in biochemistry

2020: First place overall, for poster presentation at UAMS Student Research Day

2020: Second place, Bhuvan award for excellence in biochemistry