BIOL 1101L: Fundamentals of Biology Laboratory
BIOL 1107: Principles of Biology I
BIOL 1107L: Principles of Biology I Laboratory
BIOL 3200: Genetics
BIOL 4780/BIOL 6780: Molecular Carcinogenesis
BIOL 6170: Biomolecular Techniques
Postdoctoral Fellow at the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
PhD. Biological and Biomedical Sciences; Program in Genetics and Molecular Biology, Emory University, Atlanta, GA
B.S. Biology, Minor in Classical Studies, Virginia Tech, Blacksburg, VA
I have been fly fishing since I was 11 years old, and even worked at Orvis during college teaching people about the sport. If I’m not in the lab or working on lectures you might just find me on a mountain trout stream.
Our lab focuses on the interactions between cancer cells and macrophages via the nuclear factor-kappaB (NF-κB) signaling pathway. NF-κB is a family of five transcription factors (RelA/p65, RelB, p50, p52, c-Rel) that form different dimers to regulate target gene expression in diverse biological functions, including normal immune function, synaptic plasticity, and even memory. Aberrant NF-κB activity is associated with autoimmune diseases, and importantly, cancer.
Our lab’s research efforts in the area of NF-κB signaling in glioblastoma (GBM) are part of a collaboration with Dr. Ali Arbab’s lab (Georgia Cancer Center). We have been using various models to determine the role of myeloid NF-κB on GBM growth. We have found that stimulation of GBM cell lines with bone marrow derived macrophage conditioned media from control cells, but not from cells lacking p65 (a canonical transcription factor), elevates GBM NF-κB signaling, and increases stem cell properties. We have identified that conditional deletion of canonical NF-κB signaling in myeloid cells inhibits syngeneic GBM growth, decreases CD45 infiltration into tumors, and positively influences CD8+ T cell proliferation. These data suggest that canonical NF-κB signaling has an anti-inflammatory role and is required for macrophage polarization, immune suppression, and GBM growth. Combining a NF-κB signaling inhibitor with standard therapy could improve anti-tumor immunity in GBM. More recent work focuses on production and characterization of a conditional and inducible microglial NF-κB knockout model. This model will be used to investigate the role of microglial NF-κB signaling in GBM tumor growth and resistance to treatment.
Our lab also has an interest in stromal macrophage NF-κB signaling in breast cancer. NF-κB is known to be up-regulated in breast cancer subtypes that also have high numbers of infiltrating macrophages, which are called tumor associated macrophages (TAMs). TAMs are found in many types of cancer, and can compose upwards of half of total invasive breast cancer tumor mass, which is associated with poor prognosis. The basal and claudin-low subtypes of breast cancer are very aggressive, difficult to treat, and interestingly, these subtypes are also associated with high macrophage infiltration. Microarray data indicate that NF-κB-dependent target genes are strongly upregulated in basal-like and claudin-low breast cancers, which could be due to the large numbers of infiltrating macrophages. This finding along with the fact that NF-κB can also regulate tumor stem cells makes the issue of uncovering the role NF-κB communication between TAMs and breast cancer cells very important.
Piranlioglu R, Bradford J, Arbab A. Targeting tumor microenvironment-associated cells to reverse therapy resistance. In: Cancer Sensitizing Agents for Chemotherapy. London, UK: Elsevier; 2021. Chapter 7; p.115-144.
Bhagelu Achyut, Kartik Angara, Meenu Jain, Thaiz Borin, Mohammad Rashid, Asm Iskander, Roxan Ara, Ravindra Kolhe, Shelby Howard#, Natasha Venugopal#, Paulo Rodriguez, Jennifer Bradford*, and Ali Arbab*. Canonical NF-κB signaling in myeloid cells is required for the glioblastoma growth. Scientific Reports. 2017 Oct 23;7(1):13754.
*Designates co-corresponding authors
#Designates undergraduate researchers
Sierra RA, Trillo-Tinoco J, Mohamed E, Yu L, Achyut BR, Arbab A, Bradford JW, Osborne BA, Miele L, Rodriguez PC. Anti-Jagged immunotherapy inhibits MDSCs and
overcomes tumor-induced tolerance. Cancer Research. 2017 Oct 15;77(20):5628-5638.
**A figure from this manuscript was chosen for this issue’s cover**
Bradford, JW, Baldwin, AS. IKK/Nuclear factor-kappaB and Oncogenesis: Roles in Tumor Initiating Cells and in the Tumor Microenvironment. 2014. Advances in Cancer Research. 121:125-145.
Kendellen, MF*, Bradford, JW*, Lawrence, CL, Clark, KS, Baldwin, AS. Canonical and Non-Canonical NF-κB Signaling Promotes the Function of Basal-Like Breast Cancer Tumor-Initiating Cells. 2013. Oncogene. 33(10):1297-305. * indicates co-first authors
Bradford J, Shin JY, Roberts M, Wang CE, Sheng G, Li S, Li XJ. Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington disease mice. 2010. Journal of Biological Chemistry. 285(14):10653-10661.
Bradford JW, Li S, Li XJ. Polyglutamine toxicity in non-neuronal cells. 2010. Cell Research. 20(4):400-407. Review.
Bradford J, Shin JY, Roberts M, Wang CE, Li XJ, Li S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. 2009. PNAS U.S.A. 106(52):22480-22485.
Xin ZT, Beauchamp AD, Calado RT, Bradford JW, Regal JA, Shenoy A, Liang Y, Lansdorp PM, Young NS, Ly H. Functional characterization of natural telomerase mutations found in patients with hematologic disorders. 2007. Blood. 109(2):524-32.