Joseph A. Frank, M.D.

Senior Investigator

Laboratory of Diagnostic Radiology Research

NIH Clinical Center

Building 10, Room B1N256
10 Center Drive
Bethesda, MD 20892

301-402-4314

jafrank@helix.nih.gov

Research Topics

Dr. Joseph A. Frank is an internationally known clinician scientist in the area of MRI, molecular and cellular imaging and cellular therapy. He has a longstanding clinical research focus of using MRI and Magnetic Resonance Spectroscopic Imaging as outcome measures to monitor the natural history, and using imaging metrics as outcome measures in central nervous system disease treatment trials, establishing imaging approaches as a possible surrogate marker for the new therapies. The Frank Laboratory's present major translation research interest is in the area of development of cellular and molecular imaging for use in cell and gene therapy and developing noninvasive techniques to improve cell homing and targeting to pathology. The Frank Laboratory pioneered techniques using FDA-approved superparamagnetic iron oxide nanoparticles complexed to transfection agents to magnetically label cells for cellular MRI. This method of magnetic cellular labeling is not toxic to cells and has resulted in MR imaging being used to monitor the temporal spatial migration of labeled cells as part of cellular therapy. An FDA superparamagnetic iron oxide nanoparticle complexed to transfection agents is presently being used to label genetically engineered stem cells in early phase clinical trials for treatment of patients with recurrent glioma. Plans are underway to label hematopoietic or bone marrow stromal stem cells or immune cells in patients with malignancy, ischemic or autoimmune diseases. The laboratory's translational research is also in developing techniques using high-intensity focused ultrasound to enhance homing permeability and retention of stem cells to targeted pathology. Pulsed Focused Ultrasound is a noninvasive nondestructive technique that, when coupled with cellular therapies, can be used to increase numbers of cells to targeted areas as part of regenerative medicine approach to treatment of disease. His laboratory has reported that pulse focused ultrasound induces the up-regulation and expression of chemo-attractant cytokines, growth factors and cell adhesion molecules on endothelial cells, resulting in the active homing and transmargination of stem cells from the vasculature into the targeted parenchyma. The molecular changes from pulsed focused ultrasound are due to the nonthermal acoustic radiation forces through mechanotransduction. The laboratory is actively examining the interactions of ultrasound with cellular and molecular mechanisms within normal and diseased tissues. The ability to actively home stem cells or genetically engineered cells outside or after the acute injury or inflammatory period provides additional flexibility of cell dosing and timing of cellular therapy.

Biography

Dr. Frank earned his medical degree at the State University of New York (SUNY) at Stony Brook in 1981 and trained in internal medicine at the University Hospital, Boston University Medical Center from 1981-1984. He was trained in the National Cancer Institute Medical Oncology fellowship program at NIH from 1984-85 and is board certified in internal medicine and medical oncology. Between 1985-1992 he was the Director of MRI Research in the Diagnostic Radiology Department of the NIH Clinical Center. He became a tenured senior investigator in the Clinical Center in 1989. In 1992 he moved to the Office of Intramural Research, Office of the Director, NIH, to take a position as Chief of the Laboratory of Diagnostic Radiology Research (LDRR), a congressionally- mandated program. He is now Chief of the Frank Laboratory and the Laboratory of Diagnostic Radiology Research in the Radiology and Imaging Sciences Department at the NIH Clinical Center. He is also an adjunct senior investigator in the Intramural Research Program, National Institutes of Biomedical Imaging and Bioengineering, and Director of the Imaging Sciences Training Program that is jointly sponsored with the NIH Clinical Center.

Selected Publications

  1. Kovacs ZI, Kim S, Jikaria N, Qureshi F, Milo B, Lewis BK, Bresler M, Burks SR, Frank JA. Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation. Proc Natl Acad Sci U S A. 2017;114(1):E75-E84.

  2. Burks SR, Nagle ME, Bresler MN, Kim SJ, Star RA, Frank JA. Mesenchymal stromal cell potency to treat acute kidney injury increased by ultrasound-activated interferon-╬│/interleukin-10 axis. J Cell Mol Med. 2018;22(12):6015-6025.

  3. Kovacs ZI, Tu TW, Sundby M, Qureshi F, Lewis BK, Jikaria N, Burks SR, Frank JA. MRI and histological evaluation of pulsed focused ultrasound and microbubbles treatment effects in the brain. Theranostics. 2018;8(17):4837-4855.

  4. Sinharay S, Tu TW, Kovacs ZI, Schreiber-Stainthorp W, Sundby M, Zhang X, Papadakis GZ, Reid WC, Frank JA, Hammoud DA. In vivo imaging of sterile microglial activation in rat brain after disrupting the blood-brain barrier with pulsed focused ultrasound: [18F]DPA-714 PET study. J Neuroinflammation. 2019;16(1):155.

  5. Nunes NS, Chandran P, Sundby M, Visioli F, da Costa Gon├žalves F, Burks SR, Paz AH, Frank JA. Therapeutic ultrasound attenuates DSS-induced colitis through the cholinergic anti-inflammatory pathway. EBioMedicine. 2019;45:495-510.


This page was last updated on August 13th, 2019