photo of Afshin Beheshti

Afshin Beheshti, PhD


Associate Investigator
Center of Cancer Systems Biology

Research Assistant Professor of Medicine
Tufts University School of Medicine

Email: afshin.beheshti [at] tufts.edu  or  afshin [at] cancer-systems-biology.org

Education and Training:

2000 – 2002 PhD, Biophysics Florida State University, Tallahassee, FL
1997 – 2000 MS, Physics Florida State University, Tallahassee, FL
1993 – 1997 BS, Physics University of Minnesota, Minneapolis, MN

Research Interests:

Aging Effects on Carcinogenesis
Aging has tremendous impact on cancer progression and is important to consider when assessing the carcinogenesis process and individualized cancer therapy. With increasing host age, normally robust cellular processes such as angiogenesis or immune surveillance may decrease resulting in a change in tumor-host dynamics. My interest and research is focused on the effects and mechanisms of how older hosts provide a microenvironment that facilitates slower tumor progression. Using murine tumor models at various ages along with mathematical modeling and advanced gene array/bioinformatics tools, I am able to start unraveling the mystery behind the tumor dynamics with advanced age.

images of
gene differences in different aged hosts graphic of
      cell processes

Proton and HZE Irradiation Effects with Aging on Carcinogenesis
Proton radiation is touted for improved tumor targeting, over standard gamma radiation, due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory demonstrate that in addition to targeting advantages, proton irradiation can inhibit angiogenic and immune factors critical to hallmark cancer processes and thereby modulate tumor progression. Beyond therapy, high-energy protons constitute a principal component of galactic cosmic rays followed by other type of HZE (high atomic number (Z), high energy (E)) radiation, such as 56Fe. These factors are a consideration in carcinogenesis risk for space flight. Given that proton irradiation modulates fundamental biological processes that are known to decrease with host aging, angiogenesis and immunogenicity, I am investigating how proton irradiation impacts tumor advancement as a function of host age, a question with both therapeutic and carcinogenesis implications. In addition I am also studying the effects of 56Fe irradiation as a function of host age which is a subject that has been minimally explored.

graphic of
network map graphic of
gene changes in irradiated vs unirradiated old hosts

Cell fusion has been known to occur naturally in nature in muscle formation, neurons, stem cells, and embryogenesis. With the assistance of viruses, cell fusion has also been implicated in tumorigenesis. I'm interested in tumor–cell fusion and other fusion that can take place in the natural process of tumorigenesis.

image of
cell-tumor fusion


DNA Double Strand Breaks (DSBs) have been widely studied in the radiation field. DNA DSBs occur when both strands in the double helix are severed. This is particularly hazardous to the cell because they can lead to genome rearrangements and mutations which can eventually lead to cancer. DNA DSBs can be caused by many factors such as radiation, oxidation, UV light, industrial chemicals, etc. When a DNA DSB occurs in a cell, there are two methods of repair which can occur: non-homologous end joining (NHEJ) and homologous recombination (HR). Both of these methods have proteins that become phosphorylated or recruited for the repair. Some of these repair proteins of particular interest are γ-H2AX, 53BP1, and phosphorylated ATM (psATM). As seen in the images below, these proteins all colocalize and appear as foci where there are DSBs in the nuclei of a cell. In healthy cells, there are minimal amounts of DSBs that occur in the cell (on average of less than 1 foci per cell), whereas cancer cells have a wide variety of DNA DSBs. My interest is in the interaction of these cancer cells with a naturally-elevated level of DSBs and the impact on the microenvironment.

images of
double stand breaks


Publications:
(click on title to go to manuscript abstract)