Research Knowledgebase

Mansoor M. Ahmed, Ph.D. Associate Professor of Radiation Oncology

Description of Research

Dr. Ahmed’s laboratory focuses on several projects in a multi-faceted approach, employing various novel strategies with the goal of increasing the therapeutic ratio through two broad areas: (1) the manipulation of tumor control by modulating the processes that controls cell cycle and apoptosis; and (2) the reduction of normal tissue morbidity by applying the emerging information on the molecular mechanistic basis of radiation or chemotherapeutic sensitivity.
A typical tumor has compartments of normal tissue margins, tumor epithelium and neo-vascular endothelium. For gaining optimal effects of any kind of treatment approaches, it is highly important to understand the areas pertaining to the biology of tumor epithelium with respect to gene signaling-dependent growth, biology of tumor neo-vascularization under the regulation of gene expression and the biology of the bystander normal tissue around the tumor. On this tenet, five major research focus areas have been established. They are (1) Signal transduction and apoptosis; (2) Angiogenesis and gene expression; (3) Radiation-Chemotherapy interaction and tumor microenvironment; (4) Normal tissue effects; and (5) Bio-markers of response. The above themes were applied in prostate, pancreas, lung and head & neck cancers.
In prostate tumors, Dr. Ahmed’s lab identified the functional role of Early Growth Response-1 (EGR-1) gene as marker of radiation sensitivity, with current major focus in establishing the functional role of EGR-1 partner proteins such as YAP1 and p300 in regulating radiation sensitivity.
In pancreatic tumors, there is loss of negative growth regulation by TGF-b, and hence these tumors possess aggressive proliferative phenotype. Dr Ahmed’s lab reported that restoration of TGF-b signaling reverts radiation resistance in pancreatic tumors. Particularly, restoring the expression of TGF-b type II receptor or Smad-4 (which is often dysregulated in pancreatic tumors) increases the radiation sensitivity potential of pancreatic tumors.
In addition to signal transduction research in radiation oncology, Dr. Ahmed’s lab investigated novel radiation delivery methods to enhance radiation response in head and neck tumors as well as in lung tumors. In head and neck tumors, low-dose radiation (hyper-radiation sensitivity inducing dose of radiation <0.5 Gy) was utilized to potentiate the effect of chemotherapy. Low-dose radiation effectively abrogated the induction of pro-survival factors such as NFkB, Bcl-2 and mdr-1 and upregulate concomitantly pro-apoptotic genes such as bax. Another concept that was tested in lung tumors is the use of bystander / abscopal factors induced in response to high-dose radiation. Dr Ahmed’s lab reported that TRAIL and TNF-b induce in response to 10 Gy dose of radiation potentiate the effect of chemotherapy alone treated lung cancer cells. Several clinical protocols have been developed in both low-dose radiation and high-dose radiation bystander therapeutics have been developed and recruitment of patients are ongoing across several centers in USA and UK.

Selected Cancer-Related Publications

Zagurovskaya M, Shareef MM, Das A, Reeves A, Gupta S, Sudol M, Bedford MT, Prichard J, Mohiuddin M, Ahmed MM. EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells. Oncogene 28:1121-31,2009. PubMed link

Mishra KP, Ahmed M, Hill RP. Low-dose radiation effects on human health with implications to radioprotection and cancer radiotherapy. Int J Radiat Biol 84:441-4,2008. PubMed link

Udayakumar TS, Hachem P, Ahmed MM, Agrawal S, Pollack A. Antisense MDM2 Enhances E2F1-Induced Apoptosis and the Combination Sensitizes Androgen-Dependent and Androgen-Independent Prostate Cancer Cells to Radiation. Mol Cancer Res 6:1742-54,2008. PubMed link

Ahmed MM, Sheldon D, Fruitwala MA, Venkatasubbarao K, Lee EY, Gupta S, Wood C, Mohiuddin M, Strodel WE. Downregulation of PAR-4,a pro-apoptotic gene,in pancreatic tumors harboring K-ras mutation. Int J Cancer 122:63-70,2008. PubMed link

Shareef MM, Brown B, Shajahan S, Sathishkumar S, Arnold SM, Mohiuddin M, Ahmed MM, Spring PM. Lack of P-glycoprotein expression by low-dose fractionated radiation results from loss of nuclear factor-kappaB and NF-Y activation in oral carcinoma cells. Mol Cancer Res 6:89-98,2008. PubMed link

Shareef MM, Dancea HC, Gross JL, Myers TT, Griggs WW, Ahmed MM, Sheldon DG. A noncommercial polymerase chain reaction-based method to approach one hundred percent recombinant clone selection efficiency. Anal Biochem 382:75-6,2008. PubMed link

Shareef MM, Cui N, Burikhanov R, Gupta S, Satishkumar S, Shajahan S, Mohiuddin M, Rangnekar VM, Ahmed MM. Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma. Cancer Res 67:11811-20,2007. PubMed link

Reeves A, Zagurovskaya M, Gupta S, Shareef MM, Mohiuddin M, Ahmed MM. Inhibition of transforming growth factor-beta signaling in normal lung epithelial cells confers resistance to ionizing radiation. Int J Radiat Oncol Biol Phys 68:187-95,2007. PubMed link

For full description of Multidisciplinary Research Program(s), Genitourinary Malignancies Program.