Text Image: UM Medical School: Graduate Program in Immunology
Text Image: Faculty

James R. Baker, Jr. M.D.
Ruth Dow Doan Professor
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

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

Mullen DG, McNerny DQ, Desai A, Cheng XM, Dimaggio SC, Kotlyar A, Zhong Y, Qin S, Kelly CV, Thomas TP, Majoros I, Orr BG, Baker JR, Banaszak Holl MM.  Design, synthesis, and biological functionality of a dendrimer-based modular drug delivery platform.  Bioconjug Chem 22(4), 679-89, 2011.

Huang B, Desai A, Zong H, Tang S, Leroueil P, Baker JR.  Copper-free click conjugation of methotrexate to a PAMAM dendrimer platform.  Tetrahedron Lett, 52(13), 1411-1414, 2011.

Baker JR Jr.  The need to pursue and publish clinical trials in nanomedicine.  Wiley Interdiscip Rev Nanomed Nanobiotechnol, in press, 2011.

Zhang Y, Thomas TP, Lee KH, Li M, Zong H, Desai AM, Kotlyar A, Huang B, Banaszak Holl MM,  Baker JR Jr.  Polyvalent saccharide-functionalized generation 3 poly(amidoamine) dendrimer-methotrexate conjugate as a potential anticancer agent.  Bioorg Med Chem 19(8), 2557-64, 2011.

Hamouda T, Sutcliffe JA, Ciotti S, Baker JR Jr.  Intranasal immunization of ferrets with commercial trivalent influenza vaccines formulated in a nanoemulsion-based adjuvant.  Clin Vaccine Immunol 18(7), 1167-75, 2011.

Desai AM, Andreae M, Mullen DG, Holl MM, Baker JR Jr.  Acetonitrile shortage: use of isopropanol as an alternative elution system for ultra/high performance liquid chromatography.  Anal Methods 3(1), 56-58, 2011.

Plantinga A, Witte A, Li MH, Harmon A, Choi SK, Banaszak Holl MM, Orr BG, Baker JR Jr, Sinniah K.  Bioanalytical screening of riboflavin antagonists for targeted drug deliver – a thermodynamic and kinetic study.  ACS Med Chem Lett 2(5), 363-67, 2011.

Ward BB, Dunham T, Majoros IJ, Baker JR Jr.  Targeted dendrimer chemotherapy in an animal model for head and neck squamous cell carcinoma.  J Oral Maxillofac Surg, in press, 2011. 

Thomas TP, Goonewardena SN, Majoros I, Kotlyar A, Cao Z, Leroueil PR, Baker JR Jr.  Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis.  Arthritis Rheum, in press, 2011.

Ciotti S, Baker JR, Ma LF, Eisma R.  Novel follicular-targeted nanoemulsion for acne.  J Amer Acadamy Derm 62(3), AB24-AB24 Suppl S, 2010.

Shi XY, Lee I, Chen XS, Shen MW, Xiao SL, Zhu MF, Baker JR, Wang SH.  The influence of dendrimer surface charge on the bioactivity of 2-methoxyestradiol complexed with dendrimers.  Soft Matter 6(11), 2539-2545, 2010. 

Chang Y-C, Ye JY, Thomas TP, Cao Z, Kotlyar A, Tkaczyk ER, Baker Jr JR.  Fiber-optic multiphoton flow cytometry in whole blood and in vivo.  J Biomed Optics 15(4), 1 (July/Aug), 047004, 2010.

Thomas TP, Choi SK, Li M-H, Kotlyar A, Baker Jr JR.  Design of riboflavin-presenting PAMAM dendrimers as a new nanoplatform for cancer-targeted delivery.  Bioorg Med Chem Lett 20(17), 5191-4, 2010.

Mullen DG, Borgmier EL, Fang M, McNerny DQ, Desai A, Baker Jr JR, Orr BG, Banaszak Holl MM.  Effect of mass transport in the synthesis of partially acetylated dendrimer: Implications for functional ligand-nanoparticle distributions.  Macromolecules 43(16), 6577-87, 2010.

Mullen DG, Borgmier EL, Desai AM, van Dongen MA, Barash M, Cheng X-m, Baker Jr JR, Banaszak Holl MM.  Isolation and characterization of dendrimer with precise numbers of functional groups.  Chemistry 16(35), 10675-8, 2010.

Thomas TP, Huang B, Desai A, Zong H, Cheng XM, Kotlyar A, Leroueil PR, Dunham T, van der Spek A, Ward BB, Baker JR Jr.  Plasma-mediated release of morphine from synthesized prodrugs.  Bioorg Med Chem Lett 20(21), 6250-3, 2010.

Kim JK, Shukla R, Casagrande L, Sedgley C, Nor JE, Baker JR Jr, Hill EE.  Differentiating dental pulp cells via RGD-dendrimer conjugates.  J Dent Res 89(12), 1433-8, 2010.

Majoros IJ, Ward BB, Lee KH, Choi SK, Huang B, Myc A, Baker JR.  Progress in cancer nanotechnology.  Prog Mol Biol Transl Sci 95, 193-236, 2010.

Baker JR Jr.  Induction of immune response to the 17 kDa OMPA Burkholderia cenocepacia polypeptide and protection against pulmonary infection in mice after nasal vaccination with an OMP nanoemulsion-based vaccine.  Med Microbiol Immunol 199(2), 81-92, 2010.

Makidon PE, Nigavekar SS, Bielinska AU, Mank N, Shetty AM, Suman J, Knowlton J, Myc A, Rook T, Baker JR Jr.  Characterization of stability and nasal delivery systems for immunization with nanoemulsion-based vaccines.  J Aerosol Med & Pulmonary Drug Delivery 23(2), 77-89, 2010.

Tkaczyk ER, Tkaczyk AH, Mauring K, Ye JY, Baker JR Jr, Norris TB.  Quantitation differentiation of dyes with overlapping one-photon spectra by femtosecond pulse-shaping.  J Luminescence 130(1), 29-34, 2010.

Zhang Y, Thomas TP, Desai A, Zong H, Leroueil PR, Majoros IJ, Baker JR Jr.  Targeted dendrimeric anticancer prodrug: A methotrexate-folic acid poly(amidoamine) conjugate and a novel, rapid, "one pot" synthetic approach.  Bioconjugate Chem 2010, DOI 10.1021/bc9003958.

Mullen DG, Fang M, Desai A, Baker JR Jr, Orr BG, Banaszak Holl MM.  A quantitative assessment of nanoparticle-ligand distributions: Implications for targeted drug and imaging delivery in dendrimer conjugates.  ACS Nano 4(2), 657-70, 2010.

Huang B, Desai A, Tang S, Thomas TP, Baker JR Jr.  The Synthesis of a c(RGDyK) targeted SN38 prodrug with an indolequinone structure for bioreductive drug release.  Organic Letters 12(7), 1384-7, 2010. 

McNerny D, Kukowska-Latallo J, Mullen D, Wallace J, Desai A, Shukla R, Huang B, Banaszak Holl M, Baker JR Jr.  RGD dendron bodies; synthetic avidity agents with defined and potentially interchangeable effector sites that can substitute for antibodies.  Bioconj Chem 2010, in press.

Thomas TP, Shukla R, Kotlyar A, Kukowski-Latallo J, Baker JR Jr.  Dendrimer-based tumor cell tarteting of fibroblast growth factor-1.  Bioorg Med Chem Lett 20(2), 700-3, 2010.

Qi R, Mullen DG, Baker Jr. Banaszak Holl MM.  The mechanism of polyplexes internationalization into cells: testing the GM1/caveolin-1-mediated lipid raft mediated endocytosis pathway.  Mol Pharm 7(1), 267-79, 2010.

Myc A, Kukowska-Latallo J, Cao P, Swanson B, Battista J, Dunham T, Baker JR Jr.  Targeting the efficacy of a dendrimer-based nanotherapeutic in heterogeneous xenograft tumors in vivo.  Anticancer Drugs 21(2), 186-92, 2010.

Choi SK, Thomas T, Li M-H, Kotlyar A, Desai A, Baker JR Jr.  Light-controlled release of caged doxorubicin from folate receptor-targeting PAMAM dendrimer nanoconjugate.  Chem Comm 46(15), 2632-34, 2010.

Guo Y, Ye JY, Huang B, McNerny D, Thomas TP, Baker JR Jr, Norris TB.  Real-time small molecule binding detection using a label-free photonic crystal biosensor.  Proc of SPIE, 7553, 755303, 2010, DOI: 10.1117/12.846011.

Hemmila MR, Mattar A, Taddonio MA, Arbabi S., Hamouda T, Ward PA, Wang SC, Baker JR Jr.  Topical nanoemulsion therapy reduces bacterial wound infection and inflammation after burn injury.  Surgery 2010, DOI February 26.

Bielinska AU, Gerber M, Blanco LP, Makidon PE, Janczak KW, Beer M, Swanson B, Baker JR Jr.  Induction of Th17 cellular immunity with a novel nanoemulsion adjuvant.  Crit Rev Immunol 30(2), 189-199, 2010.

Hamouda T, Chepurnov A, Mank N, Knowlton J, Chepurnova T, Myc A, Sutcliffe J, Baker JR Jr.  Efficacy, immunogenicity and stability of a novel intranasal nanoemulsion-adjuvanted influenza vaccine in a murine model.  Hum Vaccin 6(7), July 17, 2010. Epub ahead of print)

McNerny DQ, Leroueil PR, Baker JR Jr.  Understanding specific and nonspecific toxicities; a requirement for the development of dendrimer-based pharmaceuticals.  Wiley Interdiscip Rev Nanomed Nanobiotechnol 2(3), 249-59, 2010.

Guo Y, Ye JY, Divin C, Huang B, Thomas TP, Baker Jr JR, Norris TB.  Real-time biomolecular binding detection using a sensitive photonic crystal biosensor.  Anal. Chem. 82(12), 5211-5218, 2010.

Shi X, Sun K, Baker JR Jr.  Spontaneous formation of functionalized dendrimer-stabilized gold nanoparticles.  J Phys Chem C 112, 8251-8258, 2009.

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), 517-32, 2009.

Shi X, Wang SH, Van Antwerp ME, Chen X, Baker JR Jr.  Targeting and detecting cancer cells using spontaneously formed multifunctional dendrimer-stabilized gold nanoparticles.  Analyst 134(7), 1379-9, 2009.

Shi X, Wang S, Shen M, Van Antwerp M, Chen X, Li C, Petersen E, Huang Q, Weber W, Baker JR Jr.  Multifunctional dendrimer-modified multi-walled carbon nanotubes: synthesis, characterization, and in vitor cancer cell targeting and imaging.  Biomacromolecules 10(7), 1744-1750, 2009.

Ge S, Shi X, Sun K, Li C, Baker JR Jr, Banaszak Holl MM, Orr BG.  A facile hydrothermal synthesis of iron oxide nanoparticles with tunable magnetic properties.  J Phys Chem C 113(31), 13593-13599, 2009.

Kelly CV, Liroff MG, Triplett LD, Leroueil PR, Mullen DG, Wallace JM, Meshinshi S, Baker JR Jr, Orr BG, Banaszak Holl MM.  Stoichiometry and structure of poly(amindoamine) dendrimer-lipid complexes.  ACS Nano 3(7), 1886-1896, 2009.

Guo Y, Ye JY, Divin C, Thomas TP, Myc A, Begey TB, Baker JR Jr, Norris TB.  Label-free biosensing using a photonic crystal structure in a total-internal-reflection geometry.  Proc of SPIE 7188, 71880B, 2009.

Shen M, Wang SH, Shi X, Chen X, Huang Q, Petersen EJ, Pinto RA, Baker JR Jr., Weber WJ Jr.Polyethyleneimine-mediated functionalization of multi-walled carbon nanotubes:  synthesis, characterization and in vitro toxicity assay.  J Phys Chem C 113(8), 3150-3156, 2009.

Chen J, Hessler JA, Putchakayala K, Panama BK, Khan DP, Hong S, Mullen D, DiMaggio SC, Lopatin A, Baker JR Jr, Orr BG, Banaszak Holl MM.  Polymer nanoparticles induce nanoscale disruption in living cell plasma membranes.  J Phys Chem B 113(32), 11179-11185, 2009.

Hong S, Rattan R, Majoros IJ, Mullen DG, Peters JL, Shi X, Bielinska AU, Blanco L, Orr BG, Baker JR Jr, Holl MM.  The role of ganglioside GM(1) in cellular internalization mechanisms of poly(amidoamine) dendrimers.  Bioconjug Chem 20(8), 1503-1513, 2009.

Huang B, Tang S, Desai A, Cheng X, Kotlyar A, Van Der Spek A, Thomas TP, Baker JR Jr.  Human plasma-mediated hypoxic activation of indolequinone-based naloxone pro-drugs.  Bioorg Med Chem Lett 19(17), 5016-5020, 2009.

Shi X, Wang SH, Lee I, Shen M, Baker JR Jr.  Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells.  Biopolymers 91(11), 936-42, 2009.

Shi X, Sun K, Baker JR Jr.  Spontaneous formation of functionalized dendrimer-stabilized gold nanoparticles.  J Phys Chem C Nanomater Interfaces 112(22), 8251-58, 2009.

Thomas T, Majoros I, Kotlyar A, Mullen D, Banaszak Holl M, Baker JR Jr.  Cationic poly(amidoamine) dendrimer induces lysosomal apoptotic pathway at therapeutically relevant concentrations.  Biomacromolecules 10(12), 3207-14, 2009.

Majoros IJ, Williams CR, Becker AC, Baker JR Jr.  Surface interaction and behavior of poly(amidoamine) dendrimers: deformability and lipid bilayer disruption.  J Computational & Theoretical Nanoscience 6(7), 1430-1436, 2009.

Majoros IJ, Williams CR, Becker A, Baker JR Jr.  Methotrexate delivery via folate targeted dendrimer-based nanotherapeutic platform.  Wiley Interdiscip Rev Nanomed Naobiotechnol 1(5), 502-10, 2009.

Dendrimer-based nanoparticles for cancer therapy.  Baker JR Jr.  Hematology Am Soc Hematol Educ Program 2009:708-19.

Chen J, Hessler JA, Putchakayala K, Panama BK, Khan DP, Hong S, Mullen DG, Dimaggio SC, Som A, Tew GN, Lopatin AN, Baker JR, Holl MM, Orr BG.  Cationic nanoparticles induce nanoscale disruption in living cell plasma membranes.  J Phys Chem B 113(32), 11179-85, 2009.

 

 

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