James R. Baker, Jr. M.D.
Ruth Dow Doan Professor
Chief, Division of Allergy and Immunology
Department of Internal Medicine
Director, Michigan Nanotechnology Institute for Medicine and Biological Sciences

jbakerjr@umich.edu

Research Interests: Autoimmune disease; Apoptosis; nanomaterials and biology; targeted therapeutic and enhanced contrast agents; pathogen defense and inactivation; adjuvant vaccine development

Current Research Activity:

1. Dr. Baker's research in the area of autoimmune endocrine disease has helped define the basis of the autoimmune response to thyroid auto-antigens.

2. Dr. Baker's lab has developed a nano emulsion that serves as a pathogen avoidance barrier and post-exposure therapeutic agent to be applied in a topical manner to the skin and mucous membranes. Dr. Baker's work with synthetic lipid and polymeric nanostructures has resulted in the development of a new class of antimicrobial agents with activity against gram positive bacteria and spores, fungi and viruses. The scope of the original research project has now been expanded to include the study of the adjuvant and/or immuno-stimulant capabilities and mechanism of action of the nanoemulsions mixed with pathogens in animal models. pursue nanoemulsion based vaccines for Hepatitis B, Anthrax, Vaccinia, Influenza, H5N1, a Bioterrorism Trivalent vaccine covering anthrax, Botulinum toxin and plague, and for Cystic Fibrosis ( Burkholderia cepacia)

3. Dr. Baker heads the Michigan Nanotechnology Institute for Medicine and Biological Sciences ( M -NiMBS) a multidisciplinary team with scientists from the Schools of Medicine, Engineering and LS&A who work on the development of new platforms for drug delivery, most notably the development of a multi-function device for the diagnosis and treatment of cancer based on dendrimer technology. Dendrimers are tree branched polymers with a precise molecular structure, and of a size comparable to proteins. They are well tolerated by cells in vitro , and by mice in vivo .

4. M -NiMBS also develops functional MRI and SQUID imaging utilizing targeted magnetic nanoparticle contrast agents. The contrast enhancement is provided by superparamagnetic, metal containing nanoparticles based on dendritic polymers. Cellular targeting of the contrast agents is accomplished by conjugating the nanoparticles to folate molecules on the dendrimer scaffold, with binding and internalization of the contrast agents through the high-affinity folate receptor.

5. Using the dendrimer platform, M -NiMBS is developing a controlled release system of Morphine / Naloxone with a built in feedback system that controls the release of the antagonist, Naloxone, based upon the injured soldier's condition. Ideally this combination drug can be self-administered by the injured soldier on the battlefield.

Recent Publications:

Lipuma JJ, Makidon PE, Foster BK, Keoleian JC, Rathinavelu S, Kailkin LM, Baker JR Jr. In vitro activities of a novel nanoemulsion against Burkholderia and other multi-drug resistant cystic fibrosis-associated bacterial species. Antimicrob Agents Chemother 53(1), 249-55, 2009.

Chang Y-C, Ye JY, Thomas TP, Cao Z, Kotlyar A, Tkaczyk ER, Baker JR Jr, Norris TB. Two-photon in vivo flow cytometry using a fiber probe. Proc. of SPIE 7173, 717301, 2009.

Lee I, Majoros IJ, Williams CR, Athey BD, Baker JR Jr. Interactive design strategy for a multi-functional PAMAM dendrimer-based nano-therapeutic using computational models and experimental analysis. J Computational and Theoretical Nanoscience 6, 54-60, 2009.

Ge S, Shi X, Baker JR Jr, Banaszak Holl MM, Orr BG. Development of a remanence measurement-based SQUID system with in-depth resolution for nanoparticle imaging. Phys Med Biol 54(10), N177-N188, 2009.

Wang SH, Shi X, Chen X, Baker JR Jr. Therapeutic efficacy of 2-methoxyestradiol microcrystals encapsulated within polyelectrolyte multilayers. Macromol Biosci 9(5), 429-436, 2009.

Wang SH, Chen G-H, Fan Y, Van Antwerp M, Baker JR Jr. Tumor necrosis factor-related apoptosis-inducing ligand inhibits experimental autoimmune thyroiditis by the expansion of CD4+CD25+ regulatory T cells. Endocrinology 150(4), 2000-07, 2009.

Tkaczyk ER, Tkaczyk AH, Mauring K, Ye JY, Baker JR Jr, Norris TB. Control of two-photon fluorescence of common dyes and conjugated dyes. J Fluorescence 19(3), 517, 2009.

Bi X, Shi X, Baker JR Jr. Synthesis, characterization and stability of
a luteinizing hormone-releasing hormone (LHRH)-functionalized
poly(amidoamine) dendrimer conjugate. J Biomater Sci Polym Ed. 19(1),
131-42, 2008.

Desai A, Shi X, Baker JR Jr. Capillary electrophoresis of
poly(amidoamine) succinamic acid dendrimers using a polyvinyl alcohol
(PVA)-coated capillary. Electrophoresis 29, 510-515, 2008.

Bielinska AU, Janczak KW, Landers JJ, Markovitz DM, Montefiori DC,
Baker JR Jr. Nasal immunization with a recombinant HIV gp120 and
nanoemulsion adjuvant produces Th1 polarized responses and neutralizing
antibodies to primary HIV type1 isolates. AIDS Res Human Retroviruses
24(2), 271-281, 2008.

Myc A, Douce TB, Ahuja N, Kotlyar A, Kukowska-Latallo JF, Thomas TP,
Baker JR Jr. Preclinical antitumor efficacy evaluation of
dendrimer-based methotrexate conjugates. Anticancer Drugs 19(2), 143-9,
2008.

Thomas TP, Shukla R, Kotlyar A, Liang B, Ye JY, Norris TB, Baker JR Jr.
Dendrimer-epidermal growth factor conjugate displays super agonist
activity. Biomacromolecules 9, 603-609, 2008.

Thomas TP, Ye JY, Chang Y-C, Kotlyar A, Cao Z, Majoros IJ, Norris TB,
Baker JR Jr. Investigation of tumor cell targeting of a dendrimer
nanoparticle using a double-clad optical fiber probe. J Biomed Optics
13(1), 014024-1 * 014024-6, 2008.

Leroueil PR, Berry SA, Duthie K, Han G, Rotello VM, McNerny DQ, Baker
JR Jr, Orr BG, Banaszak Holl MM. Wide varieties of cationic
nanoparticles induce defects in supported lipid bilayers. Nano Letters
8(2), 420-424, 2008.

Landmark KJ, DiMaggio S, Ward J, Kelly C, Vogt S, Hong S, Kotlyar A,
Myc A, Thomas TP, Penner-Hahn JE, Baker JR Jr, Banaszak Holl MM, Orr BG.
Synthesis, characterization, and in vitro testing of superparamagnetic
iron oxide nanoparticles targeted using folic acid-conjugated
dendrimers. ACS Nano 2(4), 773-783, 2008.

Shi X, Wang SH, Swanson SD, Ge S, Cao Z, Van Antwerp M, Landmark KJ,
Baker JR Jr. Dendrimer-functionalized shell-crosslinked iron oxide
nanoparticles for in vivo magnetic resonance imaging of tumors.
Advanced Materials 20, 1671-78, 2008.

Bielinska AU, Chepurnov AA, Landers JJ, Janczak KW, Chepurnova TS,
Luker GD, Baker, JR Jr. A novel, killed-virus nasal vaccinia vaccine.
Clin Vac Immunol 15(2), 348-58, 2008.

Shi X, Lee I, Baker JR Jr. Acetylation of dendrimer-entrapped gold and
silver nanoparticles. J Mater Chem 18, 586-93, 2008.