Assistant Professor

Ph.D. University of Arizona, Tucson, AZ

M.S. McMaster University, Hamilton, ON, Canada

B.S. McMaster University, Hamilton, ON, Canada

 

E-mail: skendrick@uams.edu

Office: (501)686-5823 – Winthrop P. Rockefeller Cancer Institute, Rm. 11-121

Lab: – Winthrop P. Rockefeller Cancer Institute, Rm. 11-190

 

Lymphomagenesis and the role of DNA secondary structures and HIV-infection

Our research interest focuses on understanding the molecular mechanisms behind the genomic instability of lymphoma, in particular diffuse large B-cell lymphoma, the most commonly diagnosed, aggressive non-Hodgkin’s lymphoma, and discovering new therapeutic strategies to improve patient outcome. In order to address this important area of cancer biology, we integrate basic and translational science by utilizing ex vivo, cell line- and tumor tissue-based models, and genomic and proteomic approaches.

 

  1. Identifying mechanisms for genomic instability at critical oncogenes in lymphoma: 
AID, an enzyme involved in antibody diversity by targeting immunoglobin genes, also aberrantly causes mutations in oncogenes such as BCL2 and MYC. Why these oncogenes are susceptible to misappropriated AID activity is unknown. DNA secondary structures may act as recruiting elements and/or scaffolds for AID activity at promoter and super enhancers of oncogenes.

 

  1. Impact of HIV infection on the molecular oncogenesis of lymphoma:HIV seropositive individuals are at high-risk for developing lymphoma compared to the general population; however, underlying mechanisms for lymphomagenesis in the context of HIV infection are poorly defined. We aim to resolve the current lack in understanding the molecular biology differences between lymphoma that develops in HIV-infected and non-HIV infected patients.

 

  1. Exploring i-motifs as therapeutic targets in lymphoma and role in transcription regulation: DNA secondary structures have the potential to act as molecular switches turning gene expression “on” or “off”. Cytosine-rich DNA can form a DNA secondary structure called the i-motif during nuclear processes in which negative superhelicity (torsional stress) facilitates a single-stranded or an “open” DNA conformation. These can be very diverse structures varying in size and nucleotide sequence within the loop regions providing specific binding sites for proteins and small molecules.

 

Selected Publications:

 

Kendrick S, Muranyi A, Gokhale V, Hurley LH, Rimsza LM. (2017) Simultaneous drug targeting of the promoter MYC G-quadruplex and BCL2 i-motif in diffuse large B-cell lymphoma slows tumor growth. J Med Chem, 60:6587-97.

 

Kendrick S, Tus K, Wright G, Jaffe ES, Rosenwald A, Campo E, Chan WC, Connors JM, Braziel RM, Ott G, Delabie J, Cook JR, Weisenburger DD, Greiner TC, Fu K, Staudt LM, Gascoyne RD, Scott DW, Rimsza LM. (2016) Diffuse large B-cell lymphoma cell-of-origin classification using the Lymph2Cx assay in the context of BCL2 and MYC expression status. Leukemia and Lymphoma, 57:717-20.

 

Kendrick SL, Redd L, Muranyi A, Henricksen LA, Stanislaw S, Rosenwald A, Ott G, Gascoyne RD, Weisenburger DD, Jaffe ES, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Staudt LM, Chan WC, Steidl C, Grogan TM, Rimsza LM. (2014) BCL2 antibodies targeted at different epitopes detect varying levels of protein expression and correlate with frequent gene amplification in diffuse large B cell lymphoma (DLBCL). Human Pathology, 45:2144-53. PMCID: PMC3971877

 

Kendrick S*, Kang H-J*, Madathil M, Alam M, Agrawal P, Gokahle V, Yang D, Hecht S, Hurley L. The dynamic character of the BCL2 promoter i-Motif provides a mechanism for modulation of gene expression by compounds that bind selectively to the alternative DNA hairpin structure. J Am Chemistry Society, 136:4161-4171. PMCID: PMC3985915

 

Kang H-J*, Kendrick S*, Hecht S, Hurley L. The transcriptional complex between the BCL2 i- Motif and hnRNP LL is a molecular switch for control of gene expression that can be modulated by small molecules. J Am Chemistry Society, 136:4172-4185. PMCID: PMC3985447

 

Complete list on PubMed.