I am a fourth year student in Biochemistry and Molecular Biology

Education

Hendrix College – Bachelor of Arts in Neuroscience

Research

My research focuses on the melanocortin pathway in the brain which controls appetite, energy homeostasis, and glucose homeostasis. In this pathway, I am particularly interested in the function of the melanocortin 4 receptor (MC4R), a G protein-coupled receptor, and the effects of cholesterol loss on MC4R function. Brain cholesterol is mostly synthesized from within the brain as cholesterol in the periphery cannot cross the blood-brain barrier. Studies have found that cholesterol biosynthesis is decreased in the brain of Huntington’s Disease patients and in mouse models of Type 1 and Type 2 Diabetes. Using a drug called methyl-β-cyclodextrin (MβCD) to deplete cholesterol in a neuroblastoma cell line, I have found that cholesterol depletion impairs colocalization of MC4R with a vesicle-coating protein called clathrin and induces rapid desensitization of the receptor. Our lab is working to determine the mechanism of this desensitization and possible ways to restore MC4R function in a model of deficient brain cholesterol. In addition, to define the sub-cellular location of MC4R in a more physiological model, our lab expressed exogenous hemagglutinin-tagged MC4R (HA-MC4R) in primary neurons using Adeno-associated adenovirus type 2 (AAV2). We found that HA-MC4R was located both at the center and adjacent to post-synaptic sites containing ionotropic glutamate receptors, indicating that MC4R may be positioned to control glutamatergic signaling. My future research will determine how cholesterol depletion affects MC4R traffic and signaling at these sites.

Notable about her time as a Graduate

One of the first mini-projects that I had when starting graduate school was to subclone a plasmid encoding for a fluorescently-tagged G protein, Gs, which activates adenylyl cyclase. After several failed attempts and at least three months of work, I finally subcloned a plasmid that worked. Because of those failed attempts (and good record-keeping of what worked and what didn’t), I became better at subcloning and teaching others what I had learned.

Career Goals

In whatever research capacity I am involved in after the PhD, I want to continue studying neurobiology of the brain and pathology of neurodegenerative diseases and ageing and to identify possible therapeutics for improving brain function.

Experiment or technique you would most like to do

Electrophysiology—I have never done it but would like to some day!

Fun facts

I started figure skating when I was four years old, and when I’m not in the lab I am on the ice coaching my skating students.

Publications

1. Trentzsch M, Nyamugenda E, Miles TK, Griffin H, Russell S, Koss B, Cooney KA, Phelan KD, Tackett AJ, Iyer S, Boysen G, Baldini G. Delivery of phosphatidylethanolamine blunts stress in hepatoma cells exposed to elevated palmitate by targeting the endoplasmic reticulum. Cell Death Discov. 2020 Feb 18;6:8.
2. Nyamugenda E, Griffin H, Russell S, Cooney KA, Kowalczyk NS, Islam I, Phelan KD, Baldini G. Selective Survival of Sim1/MC4R Neurons in Diet-Induced Obesity. iScience. 2020 May 22;23(5):101114.
3. Griffin H, Sullivan SC, Barger SW, Phelan KD, Baldini G. Liraglutide Counteracts Endoplasmic Reticulum Stress in Palmitate-Treated Hypothalamic Neurons without Restoring Mitochondrial Homeostasis. Int J Mol Sci. 2022 Dec 30;24(1):629.

Awards

2024 – Received first place for the Bhuvan Award for Excellence in Biochemistry Research at UAMS Student Research Day

I am a 4th year student in Biochemistry and Molecular Biology

Education

Arkansas Tech University – Bachelor of Science in Biology, Bachelor of Arts in Music, Minor in Chemistry

Research

My graduate work aims to expand current knowledge on the regulation of the double stranded break response. Specifically, I study the histone H2AX and how it interacts with downstream components of the DNA damage response. Recently, I have been working to characterize a non-canonical mechanism of 53BP1 recruitment to sites of DNA damage which we found is mediated by the H2AX C-terminal linker region.

Notable about her time as a Graduate

I have been fortunate to attend multiple scientific conferences during my graduate studies. Before the conferences, I was so nervous about presenting at the poster sessions. However, once I got started, I realized that poster sessions are a lot of fun. It’s a great way to meet other scientists that are interested in your work, get input and new ideas, and geek out. So now, I look forward to presenting at poster sessions and getting to discuss my research with new people in a relaxed setting.

Career Goals

Once I obtain my PhD I will continue to pursue a career in cancer research.

Experiment or Technique most like to do

One of my favorite techniques in the lab is cloning. Prior to and during my graduate studies, I did a lot of synthetic biology to develop plasmids for my projects. I really enjoy piecing things together or changing sequences to make something entirely new.

Fun Facts

I do MMA and Brazilian Jiu Jitsu, and I have a black belt in Taekwondo. While I don’t practice as much as I used to (life is busy), I still spend many evenings wrestling my two- and four-year-old.

Publications

1. Lee SO, Kelliher JL, Song W, Tengler K, Sarkar A, Dray E, Leung JWC. UBA80 and UBA52 fine-tune RNF168-dependent histone ubiquitination and DNA repair. J Biol Chem. 2023 Jul 12;:105043. doi: 10.1016/j.jbc.2023.105043. [Epub ahead of print] PubMed PMID: 37451480.
2. Kelliher J, Ghosal G, Leung JWC. New answers to the old RIDDLE: RNF168 and the DNA damage response pathway. FEBS J. 2021 Apr 2;. doi: 10.1111/febs.15857. Review. PubMed PMID: 33797206; PubMed Central PMCID: PMC8486888.
3. Kelliher JL, West KL, Gong Q, Leung JWC. Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination. Nat Commun. 2020 May 18;11(1):2462. doi: 10.1038/s41467-020-16307-4. PubMed PMID: 32424115; PubMed Central PMCID: PMC7235047.
4. Pont MJ, Hill T, Cole GO, Abbott JJ, Kelliher J, Salter AI, Hudecek M, Comstock ML, Rajan A, Patel BKR, Voutsinas JM, Wu Q, Liu L, Cowan AJ, Wood BL, Green DJ, Riddell SR. γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019 Nov 7;134(19):1585-1597. doi: 10.1182/blood.2019000050. PubMed PMID: 31558469; PubMed Central PMCID: PMC6871311.
5. West KL, Kelliher JL, Xu Z, An L, Reed MR, Eoff RL, Wang J, Huen MSY, Leung JWC. LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation. Nucleic Acids Res. 2019 Jul 9;47(12):6236-6249. doi: 10.1093/nar/gkz263. PubMed PMID: 30982887; PubMed Central PMCID: PMC6614850.

Awards

2022 – Awarded a $1500 travel grant through the WPRCI Cancer Research Training and Education Core

2023 – Awarded a $5161 Voucher through the WPRCI Shared Resource Voucher Program

2023 – Received 1^st place for the Bhuvan Award for Excellence in Biochemistry Research at UAMS Student Research Day

2023 – Received award for Best Graduate Student Poster at the WPRCI Cancer Institute Retreat

I just started my sixth year in Biochemistry and Molecular Biology Ph.D. program and will graduate in October.

Education

China Pharmaceutical University, B.S. in Pharmacy (Basic Pharmacy).

Research

I have two research interests: 1) Discovery and optimization of novel inhibitors of clinically relevant targets 2) PROTAC and its applications. I have been working on multiple research projects within these research scopes.

I’m currently working on my dissertation thesis based on one of the projects, titled: Identification of Imidazo[1,2 a]pyridine pyridine derivatives as FLT3 kinase inhibitors for potential treatments of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematologic cancer characterized by proliferative, clonal, abnormally differentiated, and occasionally poorly differentiated cells. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most frequent genetic alteration in AML, found in approximately 30% of newly diagnosed cases, most commonly consisting of internal tandem duplication (ITD) mutations in the juxtamembrane region. Recently, several FLT3 inhibitors have demonstrated clinical activity and three are currently approved – midostaurin, quizartinib, and gilteritinib. However, their clinical efficacies are limited in part due to the emergence of secondary clinical resistance, caused by multiple mechanism including on-target FLT3 secondary mutations – FLT3-ITD/D835Y and FLT3-ITD/F691L being the most common, as well as the off-target activation of alternative pathways including the BCR-ABL pathway. Therefore, in order to overcome drug resistance and further improve outcomes, new compounds targeting FLT3-ITD with secondary mutants are urgently needed. In my works, three compounds were identified with potent anti-leukemic effects, and may be further developed for treatment of AML.

Notable about his time as a Graduate

Throughout my Ph.D. periods, I got to know that research is never a solitary work. It requires frequent communication and close collaboration to get the work done.

Career Goals

I will seek postdoc training after my Ph.D. I have already accepted the postdoc offer at Dana-Farber Cancer Institute, Harvard Medical School, working with Dr. Jun Qi. My vision for my future career is to take on the academic path and be an independent principal investigator after the postdoc training.  

Experiment or technique you would most like to do (could be something you enjoy doing or something you have never done but would like to get the opportunity to do)

I like the design and synthesis of new compounds because there is a sense of satisfaction in creating something new.

Fun Fact about Xiuqi

I like hiking and exploring nature.

Katie is a fifth year student in the Biochemistry and Molecular Biology Ph.D program.

She attended Liberty University where she completed a Bachelor of Science degree in biology with a minor in chemistry

Research Interest

My research focus is on the conserved RNA-binding protein Musashi, the proteins it associates with, and the effect those associations have on regulating translation. Musashi is a biomarker for stem cells, regulating asymmetrical differentiation and maintaining a stem cell population. Originally studied as a translational repressor, the MacNicol lab has found that Musashi is required for the translational activation of specific transcripts. However, while Musashi uses its two N-terminal RNA-recognition motifs to bind to RNA, its C-terminus is disordered and contains no enzymatic or catalytic domains. Therefore, Musashi must require protein interactions in complexes to regulate translation, the composition of which could regulate Musashi-dependent translational effects. One of those proteins is Lsm14B. We are one of the first labs to identify Lsm14B as a translational activator, and the first group to identify the Musashi:Lsm14B interaction to be necessary to translate Mos and Cyclin B5 proteins in Xenopus oocytes to re-initiation of the cell cycle as well as translating the pituitary development-specific transcription factor Prop1. I have also discovered over 200 proteins that likely associate with Musashi independent of RNA in the mouse anterior pituitary through immunoprecipitations and mass spectrometry. My research will lay the groundwork for future investigations into the regulation of Musashi-bound RNA transcripts due to Musashi-protein interactions.

Notable about her time as a graduate student

Being a Ph.D. student is already a unique experience – a global pandemic in the middle of your Ph.D. truly makes it even more unique. The amount of personal growth I have experienced not only through the usual Ph.D. experience but also through these universally trying times has affected my approach to science and my research goals, highlighting the need for good science and excellent communication.

Her career goals

I will be expanding my research training and experience through a post-doctoral research position here at UAMS.

Experiment or technique she would most like to do

I would love to learn how to conduct bioinformatics analyses.

Fun fact about Katie

I joke that I’m preparing my retirement hobbies – I love gardening, crochet, reading, and tennis. A goal of mine is to have a library of books I’ve already read.

Congratulations to Mason McCrury, a Ph.D. student in the lab of Dr. Samantha Kendrick, for receiving a NSF-GRFP. The Graduate Research Fellowship Program supports outstanding graduate students who have demonstrated the potential to be high achieving scientists and engineers. Mason’s project is entitled “Investigating DNA Secondary Structure Formation and Mutagenesis.”

Clai is a 6th year MD/Ph.D student in her 4th year in the Biochemistry and Molecular Biology Department in the laboratory of Dr. Alan Tackett and Dr. Isabelle Racine Miousse

She has a BS in Chemistry from Southern Arkansas University

Research Interest Statement

Immune checkpoint inhibitor therapy has drastically improved outcomes in treating cancer, particularly in melanoma. However, half of melanoma patients are resistant to treatment. One mechanism used by tumor cells to evade immune attack is to down-regulate major histocompatibility complex (MHC) class I molecules, which are required for cytotoxic CD8⁺ T-cells to eliminate cancer cells. To increase immunotherapeutic efficacy, it is critical to identify how to restore MHC-I expression on cancer cells so that tumor antigens are presented. We found that resveratrol elevated MHC-I expression, thereby improving CD8⁺ T-cell killing. Through proteomic interrogation, we identified the STING pathway as a potential mechanism of action. Further studies indicated that resveratrol-mediated STING signaling induced MHC-I expression through both interferon-independent and dependent pathways. Our results have uncovered the ability of STING to induce MHC-I expression independent of interferon signaling, broadening the potential of STING activation as a tool to improve immune checkpoint blockade.

Something Notable about Time as a Graduate Student

On my desk I have two quotes, one is from Joan Didion from The Year of Magical Thinking (“Read, learn, work it up, go to the literature. Information is control) and the other is from Merlin Sheldrake from Entangled Life (“What’s astonishing is the gulf between what we expect to find and what we find when we actually look”). Over the course of my studies, I’ve learned that being a scientist is an interplay between empowering yourself to ask good questions through information and expecting that the answers could be far away from what you imagined. I’m taking Didion’s quote a bit out of context for my purposes, but I relate to it in context as well.

Career Goals

As an MD/PhD student, my immediate tasks proceeding my PhD are returning to medical school to finish my medical education and then moving on to medical residency. My goal is to match into a dermatology residency program. I would like to continue contributing to research throughout the rest of my medical training. Post-residency, I plan on seeking an academic position and splitting my time between clinic and research. I would like to focus on inflammatory skin diseases and clarify targetable pathways for treatment. Health equity is also important to me. Currently I’m reading Health Communism by Artie Vierkant and Beatrice Adler-Bolton, and it really forces me to reconcile to the negative social processes that my fields help enable. When I become a physician-scientist, using my insight on both fields and how they serve as a source of knowledge and beneficence but also of capital, I plan on being involved in work progressing social justice initiatives to reach better health for all.

Experiment or Technique You would Most Like to Do

Honestly, I’m less interested in the performance of the experiments themselves, I’m more so into developing questions and plans to answer them. So, I’d like to do whatever answers the question.

Fun Fact

I like kpop; I can list all 22 members of NCT in age-order! I implore you to listen to “Sticker” by NCT 127.

Publications

The evolving clinical landscape for dendritic cell vaccines and cancer immunotherapy MJ Cannon, MS Block, LC Morehead, KL Knutson Immunotherapy 11 (2), 75-79

Further clinical advancement of dendritic cell vaccination against ovarian cancer LC Morehead, MJ Cannon Annals of research hospitals 2

Differences in cell death in methionine versus cysteine depletion KF Wallis, LC Morehead, JT Bird, SD Byrum, IR Miousse Environmental and molecular mutagenesis 62 (3), 216-226

Awards

Best Talk – 35^th National MD/PhD Conference Diversity Award – 35^th and 37^th National MD/PhD Conference Melanoma Research Foundational Medical Student Award