Staff Physician
Associate Director of Translational Research
Co-Director of the NanoBiotechnology Center
Director of Basic and Translational Radiation Research
Residency Program Director
Associate Professor
Department of Radiation Medicine
Roswell Park Cancer Institute

Associate Professor
Department of Radiation Medicine
State University of New York at Buffalo

Dr. Mohamed K. Khan joined the staff at Roswell Park Cancer Institute (RPCI) in 2004. He is an Attending Physician, the Director of Basic and Translational Radiation Research, co-director and founder of the NanoBiotechnology Center at RPCI, and the Residency Program Director in the Department of Radiation Medicine. He also serves as Associate Professor in the Department of Radiation Medicine at the University at Buffalo.

Dr. Khan earned his doctoral degree (PhD) in Biochemistry and Molecular Biology from the University of California-Santa Barbara in 1993. He completed his medical degree (MD) from the University of Chicago-Pritzker School of Medicine in 1994. He did his internship training in Internal Medicine and Surgery at the Newton-Wellesley Hospital, Newton, MA, and completed his residency in Radiation Oncology at Harvard’s Joint Center for Radiation Therapy (Brigham and Women’s Hospital, Dana Farber Cancer Institute, Boston Children’s Hospital, and Beth Israel-Deaconess Medical Center) in Boston, MA. During this time he also completed a research fellowship with Dr. Judah Folkman focused on the systemic affects of radiation on angiogenesis and tumor growth through Harvard University at Children’s Hospital, Boston, MA. Dr. Khan then proceeded to the University of Michigan where he treated radiation oncology patients at the Ann Arbor VA Healthcare System, and conducted basic and translational cancer research focused on tumor angiogenesis, nanotechnology, and radiation therapy at the University of Michigan Medical Center. He has greatly expanded much of this work upon coming to RPCI.

Dr. Khan’s research focuses on tumor angiogenesis, nanotechnology, and radiotherapy.

A) Dendrimer Nanocomposites in Radiotherapy and Imaging of the Tumor Microvasculature:
Nanotechnology is by its nature very multidisciplinary. Dr. Khan (biology) and Dr. Lajos Balogh (materials sciences, engineering) are the Co-Directors of the NanoBiotechnology Center at RPCI, where research is done involving several collaborative researchers. In the nanotechnology research, Dr. Khan and Balogh focus on both tumor imaging and therapy using composite nanodevices (CNDs) that exploit differences between the normal and tumor microvasculature. The composite nanodevices have a dendrimer 3-D polymer component with an external surface that can be use for targeting or placement of agents to attack cancer, and the “inner” region traps inorganic materials again that can be used for imaging and therapy (for example the CNDs can deliver radiation dose at level at least a log fold more that that seen with radioactive antibody therapies). One set of experiments in the laboratory attempts to send nanocomposites through the leaky tumor microvasculature and into cancer tissue in mouse tumor mouse tumor model systems, and examines important effects produced by small changes in nanodevice size or charge. The second major area is attempting to design and test nanocomposites targeted directly at the leaky tumor microvasculature, and to utilize this for multi-level imaging (whole animal, intra-tumoral, intracellular) using the same nanodevice. These are also being developed for therapy, as the metal (or Isotopes) carried by the nanodevices can be used for the delivery of radiation dose to the tumor microvasculature.

B) Tetrathiomolybdate (TM) and Radiotherapy:
His laboratory has also completed preclinical experiments demonstrating that the combination a novel anti-angiogenic agent (tetrathiomolybdate or TM) with radiation therapy will slow tumor growth better that either therapy used alone in mouse model systems. TM is an orally administered agent was shown to reduce copper levels in patients safely by Dr. George Brewer. Copper reduction has been shown to block angiogenesis, by affecting multiple pro-angiogenic molecules (bFGF, VEGF, IL-6, IL-8, angiogenic), making it a “multi-hit” anti-angiogenic agent. It has also been shown to slow tumor growth (in the laboratories of Dr. Khan, Dr. Merajver, and others). His research will now enter the clinic, with a recently NIH approved and funded phase I clinical trial to combine TM with radiotherapy in non-small cell lung carcinoma patients. As part of this research, markers linked with TM’s anti-angiogenic action will be monitored, and an imaging study will be carried out to examine whether non-invasive means of demonstrating the anti-angiogenic action of the drug in patients can be found, and assist in future trials.

C) Multi-gene Molecular Analysis (Microarray) of Angiogenic Human Endothelial Cells:
Dr. Khan’s laboratory continues to develop systems to permit the molecular analysis of angiogenesis in specifically engineered tumor microenvironments. This is done in an angiogenesis system developed by Drs. Nor, Polverini, Mooney, and Khan, where human endothelial cells are seeded onto a bioengineered matrix, implanted in SCID mice, and then undergo angiogenesis. His laboratory has developed techniques to extract the human endothelial cells from the scaffold for Microarray (multi-gene) analysis. Tumor cells can be added with the human endothelial cells, permitting the formation of multiple tumor microenvironments. The concept is to create any tumor microenvironment desired in vivo, permit human endothelial cells to undergo angiogenesis in these microenvironments, and examine the message patters during the process of tumor angiogenesis with or without various therapies (chemotherapy, radiation, etc.).

Dr. Khan is a member of the American College of Radiation Oncology, American Society for Therapeutic Radiology and Oncology, the American College of Radiology, the American Association of Cancer Research, the Radiation Research Society, the American Medical Association, the Michigan State Medical Society, and The Erie County Medical Society. Within the American Medical Association (AMA), Dr. Khan serves on the prestigious AMA Council on Science and Public Health (CSAPH), playing a leadership role on numerous scientific issues confronting all of American medicine.

Dr. Khan has authored or co-authored more than 40 journal publications, book chapters and abstracts. He is the Associate Editor for the American Journal of Clinical Oncology and an Ad Hoc Reviewer for Neoplasia, Journal of Clinical Oncology, Oncology, and AACR's Cancer Research.

 

Selected Publications
A) Nanotechnology

• Mohamed K. Khan, Shraddha S. Nigavekar, Leah D. Minc, Muhammed S. T. Kariapper, Bindu M. Nair, Wojciech G. Lesniak, Lajos P. Balogh. In Vivo Biodistribution of Dendrimers and Dendrimer Nanocomposites - Implications for Cancer Imaging and Therapy, Technology in Cancer Research and Treatment 2005; 4 (6): 603-613.
• Kukowska-Latallo JF, Candido KA, Cao Z, Nigavekar SS, Marjoros IJ, Keszler B, Thomas TP, Balogh LP, Khan MK and Baker JR. Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer, Cancer Research 2005; 65 (12): 5317-24.
• Nigavekar SS, Sung LY, Llanes M, El-Jawahri A, Lawrence TS, Becker CW, Balogh L, Khan MK. 3H dendrimer nanoparticle organ/tumor distribution. Pharm Res. 2004 Mar; 21(3):476-83
• Lajos P. Balogh, Shraddha S. Nigavekar, Andrew C. Cook, Leah Minc, and Mohamed K. Khan. Development of Dendrimer-Gold Radioactive Nanocomposites to Treat Cancer Microvasculature. PharmaChem 2003; 2(4), 94-99.
• Balogh L, Bielinska A, Eichman JD, Valluzzi R, Lee I, Baker JR, Lawrence TS and Khan MK. Dendrimer Nanocomposites in Medicine. Chimica Oggi (Chemistry Today) 2002; 20 (5): 35-40.

B) Anti-angiogenic Therapy and Radiotherapy - TM and RT

• Mohamed K. Khan, Fatema Mamou, Matthew J. Schipper, Kerstin S. May, Alla Kwitny, Amber Warnat, Brian Bolton, Bindu M. Nair, Muhammed S. T. Kariapper, Meredith Miller, George Brewer, Daniel Normolle, Sofia Merajver and Theodoros Teknos. Combination of Tetrathiomolybdate and Radiation in a Mouse Model of HNSCC. Arch Otolaryngol Head Neck Surg. 2006; 132 (3): 333-338
• Fatema Mamou, Kerstin S. May, Matthew J. Schipper, Navkiranjit Gill, Muhammed S. T. Kariapper, Bindu M. Nair, George Brewer, Daniel Normolle and Mohamed K. Khan. Tetrathiomolybdate Blocks bFGF- but not VEGF- Induced Incipient Angiogenesis in vitro. Anticancer Research 2006; 26: 1753-1758.
• Khan MK, Miller MW, Taylor J, Gill NK, Dick RD, Van Golen K, Brewer GJ, Merajver SD. Radiotherapy and antiangiogenic TM in lung cancer. Neoplasia. 2002 Mar-Apr; 4(2):164-70.

C) Angiogenesis and Microarray - Scaffold Model Development

• Nor JE, Peters MC, Christensen JB, Sutorik MM, Linn S, Khan MK, Addison CL, Mooney DJ, Polverini PJ. Engineering and characterization of functional human microvessels in immunodeficient mice. Lab Invest. 2001 Apr; 81(4):453-63.

D) Other

• Yu Y, Moulton KS, Khan MK, Vineberg S, Boye E, Davis VM, O'Donnell PE, Bischoff J, Milstone DS. E-selectin is required for the antiangiogenic activity of endostatin. Proc Natl Acad Sci U S A. 2004 May 25; 101(21):8005-10. Epub 2004 May 17.
• Camphausen K, Moses MA, Beecken WD, Khan MK, Folkman J, O'Reilly MS. Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res. 2001 Mar 1; 61(5):2207-11.