Giulia Baldini, M.D., Ph.D., professor in the Department of Biochemistry and Molecular Biology was selected as one of four inaugural recipients of the Provost’s Innovator Awards. Dr. Baldini is studying a potential new way to treat obesity. Her research is focused on naturally occurring genetic mutations of a receptor found in people with obesity. The receptor is expressed in the hypothalamus, where it controls food intake and energy expenditure. Baldini is targeting the receptor using nanoparticles to deliver a substance that induces appropriate signaling to help regulate weight.
News
Congratulations Dr. Edwards-Azumara!
Congratulations to Andrea Edwards-Azumara who successfully defended her Ph.D. dissertation entitled “Unpaired Regions in G-Quadruplex DNA Regulate “PARP-1 Enzymatic Activation: Implications for a ROS-Directed Transcription and DNA Repair Event” on February 18th. Andrea was a student in the laboratory of Dr. Kevin Raney and is now a post-doctoral fellow at UT Southwestern under the direction of Dr. William Kraus. A summary of her research is below.
G-Quadruplexes are non-B form DNA structures present at regulatory regions in the genome, such as promoters of proto-oncogenes and telomeres. The prominence in such sites suggests G-quadruplexes serve an important regulatory role in the cell. Indeed, oxidized G-quadruplexes found at regulatory sites are regarded as epigenetic elements and are associated with an interlinking of DNA repair and transcription. PARP-1 binds damaged DNA and non-B form DNA, where it covalently modifies repair enzymes or chromatin-associated proteins respectively with poly(ADP-ribose) (PAR). PAR serves as a signal in regulation of transcription, chromatin remodeling, and DNA repair. PARP-1 is known to bind G-quadruplexes with stimulation of enzymatic activity. We show that PARP-1 binds several G-quadruplex structures with nanomolar affinities, but only a subset promote PARP-1 activity. The G-quadruplex forming sequence found in the proto-oncogene c-KIT promoter stimulates enzymatic activity of PARP-1. The loop-forming characteristics of the c-KIT G-quadruplex sequence regulate PARP-1 catalytic activity, whereas eliminating these loop features reduces PARP-1 activity. Oxidized G-quadruplexes that have been suggested to form unique, looped structures stimulate PARP-1 activity. Our results support a functional interaction between PARP-1 and G-quadruplexes. PARP-1 enzymatic activation by G-quadruplexes is dependent on the loop features and the presence of oxidative damage.
Samantha Kendrick featured in Lymphoma Research Foundation magazine
Samantha Kendrick, Ph.D. is featured in on pages 24-25 the quarterly issue of the Lymphoma Research Foundation Pulse magazine for a discussion of her research on diffuse large B-cell lymphoma.
UAMS’s Justin Leung, Ph.D., Receives $792,000 American Cancer Society Grant to Study DNA Repair Mechanisms
“Understanding the molecular processes of DNA repair can help both better diagnose cancer and to progress treatment,” said Leung, an assistant professor in the UAMS College of Medicine Department of Radiation Oncology.
The grant will investigate how signaling molecules on chromatin interact with proteins that repair broken DNA during replication.
“Our DNA encounters damage every day from metabolic byproducts, toxic chemicals and ultraviolet radiation in sunlight. Unrepaired DNA damage can lead to accumulation of mutations, which can cause cancer,” Leung explained. “Our lab aims to understand how cells precisely repair DNA damage at the right place and right time. We study how the DNA damage response is initiated and the mechanism by which DNA repair proteins are brought to the DNA breaks.”
The Research Scholar grant specifically will investigate the regulatory mechanism between a signal on newly replicated DNA and how it brings a specific chromatin modifying enzyme to direct repairs at the site of DNA break at the right time by altering the damaged DNA and proteins landscape.
The new grant follows a $1.9 million funding award in September 2020 from the National Institute of General Medical Sciences supporting Leung’s roadmap project, “Deciphering the Chromatin-based DNA Damage Response Pathway.”
January publications
The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure.
Brown SL, Kendrick S. Pharmaceuticals (Basel).
Alkam D, Jenjaroenpun P, Ramirez AM, Beenken KE, Spencer HJ, Smeltzer MS. Infect Immun.
Klejborowska G, Urbaniak A, Maj E, Wietrzyk J, Moshari M, Preto J, Tuszynski JA, Chambers TC, Huczyński A. Bioorg Med Chem.
Dr. Tackett presenting for Research Antipasto
Alan Tackett, PhD will host Research and Innovation’s 1st gathering for informal networking, casual mentoring at noon on March 2, 2021. The 1st Tuesday of each month, Research Antipasto’s host will share career experiences, stories, answer questions, advise, astound, and amaze…for 20 – 30 minutes. Just show up, have fun, and get to know others in the research community! Hosts will be posted on the research calendar.
Congratulations Dr. Alkam!
Congratulations to Duah Alkam who successfully defended her Ph.D. dissertation entitled “Using genome-wide transposon sequencing (TnSeq) to identify osteomyelitis-critical Staphylococcus aureus genes” on January 28th. Duah was a student in the laboratories of Dr. Mark Smeltzer and Dr. David Ussery and is now working as in the UAMS Bioinformatics Shared Resource under the direction of Dr. Stephanie Byrum.
Dr. Diekman honored for teaching excellence
Congratulations to Alan Diekman who was recently awarded a College of Medicine Teaching Excellence Award.
Top Five Article
An article by Dr. Giulia Baldini, Professor of Biochemistry and Molecular Biology, and Dr. Kevin Phelan, Professor of Neurobiology and Developmental Sciences, was one of the top five most-cited articles in the Journal of Endocrinology in 2020. Dr. Baldini and Dr. Phelan coauthored “The melanocortin pathway and control of appetite – progress and therapeutic implications,” which was published in April 2019. Congratulations.
Welcome Dr. Miah
Sayem Miah, Ph.D. is a new Assistant Professor in the Biochemistry and Molecular Biology Department.
Research statement
My research vision is to understand how cells perceive signals that vary in healthy and cancer cells and how this perception regulates tumorigenesis and metastasis. My lab will undertake a “systemwide” interrogation of signaling networks using innovative proteomic, biochemical, and genomic techniques – to uncover how the cell decodes information within complex and combinatorial signals. We will apply these approaches to quantitatively understand healthy and cancer cell signaling in cellular decisions. For example, a long-standing biological paradox is that TGFβ signaling, which is thought to be anti-metastatic, can switch to promoting metastasis. But how the anti-metastatic function of TGFβ/SMAD signaling switches to a metastasis promoting factor is poorly understood.
Recently, we reported that breast tumor kinase (BRK), a non-receptor tyrosine kinase (nRTK), which is an oncogene and highly expressed in ~85% of human invasive ductal carcinomas, promotes metastatic potential by phosphorylating SMAD4 in mammary epithelial cells. Another family member of nRTKs, Src phosphorylates TGFβ type II receptor to promote tumor growth and metastasis. Additionally, PEAK1, induces EMT and metastasis in breast cancer cells via TGFβ/SMAD signaling.
This makes nRTKs a viable and promising target for tackling metastatic cancer—if only we knew which specific kinases needed to be targeted in order to block metastatic progression.
Opportunities for collaboration
I am highly collaborative in nature. I want to see your science and mine flourish. Please reach out if I can contribute in your science, or you in mine.
Fun fact about yourself
I never say no to coffee.
Favorite place you’ve lived
I spent first 12 years of my life in a rural village in Bangladesh. It was a full of life and close to nature.
Favorite food
Any Mediterranean food
What you like to do for fun
I love to play Ping-Pong and Soccer.