Lam, Kit S. - University of California, Davis - Department of Biochemistry and Molecular Medicine

研究领域

Dr. Lam is an expert in combinatorial chemistry, chemical biology, drug development, molecular imaging, nanotherapeutics and medical oncology. His laboratory is engaged in the development and application of combinatorial library methods for basic research and drug discovery. In addition to cancer drug development, he is also interested in signal transduction, antibiotics development, molecular immunology, chemical microarray, and proteomics. Dr. Lam is both a practicing medical oncologist and a laboratory investigator. He is distinguished for revolutionizing cancer diagnosis and treatment and is acclaimed for his pioneering role in the field of combinatorial chemistry and developing the novel one-bead-one-compound technology, which rapidly screens millions of chemicals at one time to identify those that bind to diseased cells. The tool is advancing the early detection and precise delivery of treatments for brain, breast, prostate, pancreatic, lymphoma and other cancers. In addition, it is advancing the discovery of imaging agents that produce highly detailed molecular profiles of diseases for improved diagnosis and tracking medication effectiveness. His development and applications of combinatorial chemistry and other chemical methods look to solve many biomedical problems. Dr. Lam invented the “one-bead-one-compound” (OBOC) combinatorial library method, filed the patents (The basic patents on the OBOC technology was issued in 1996, 1997, and 1999 by the US patent office), and published the technique in Nature in 1991. This represents one of the first few reports in the new field of combinatorial chemistry at the time. Since then, the field of combinatorial chemistry has rapidly evolved into a new chemistry discipline, and four scientific journals are now devoted to this field (J of Combinatorial Chemistry, Combinatorial Chemistry and Highthroughput Screening, Molecular Diversity, and QSAR Combinatorial Science). Combinatorial chemistry has become an indispensable tool in drug development and chemical research. The OBOC combinatorial library approach is unique and truly an ultra-high throughput method, as thousands to millions of chemical compounds (peptides, peptidomimetics, small molecules, and macrocyclic natural product like molecules) can be efficiently synthesized and screened in parallel in a relatively short time. Combinatorial chemistry has also provided strong impetus for the new field of “chemical genetics”. In addition to expanding the use of one-bead-one-compound technology, Dr. Lam's research also includes developing a blood test for ovarian-cancer detection, utilizing nanoparticle carriers for drug delivery and synthesizing cancer-fighting molecules with less-toxic side effects. He is currently collaborating on projects to identify the molecular pathogenesis of and treatments for primary biliary cirrhosis, osteoporosis and Alzheimer's disease.

近期论文

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Lac D, Feng C, Bhardwah G, Le H, Tran J, Xing L, Fung G, Liu R, Cheng H, Lam KS. Covalent chemical ligation strategy for mono- and polyclonal immunoglobulins at their nucleotide binding sites. Bioconjugate chemistry 2015. PMID: 26630124. Awasthi S, Izu L, Mao Z, Jian Z, Landas T, Lerner A, Shimkunas R, Woldeyesus RA, Bossuyt J, Wood BM, Chen YJ, Matthews DL, Lieu DK, Chiamvimonvat N, Lam KS, Chen-Izu Y, Chan JW. Multimodal SHG-2PF imaging of microdomain Ca2+-contraction coupling in live cardiac myocytes. Circ Res 2015. PMID: 26643875 Wang Y, Xiao W, Zhang Y, Meza L, Tseng H, Takada Y, Ames JB and Lam KS. Optimization of RGD containing cyclic peptides against αvβ3 integrin. Mol Cancer Therapeutics, Dec 30, 2015. PMID: 26719578 Smith ZJ, Lee C, Rojalin T, Carney RP, Hazari S, Knudson A, Lam K, Saari H, Ibanez EL, Vitala T, Laaksonen T, Yliperttula M, and Wachsmann-Hogiu S. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content. Journal of Extracellular Vesicles. In press Nov 2015 Zhang P, Zam A, Jian Y, Wang X, Ki Y, Lam KS, Burns ME, Sarunic MV, Pugh EN and Zawadzki RJ. In vivo wide-field multispectral SLO-OCT mouse retinal imager: longitudinal imaging of ganglion cells, microglia and Müller glia, and mapping of the mouse retinal and choroidal vasculature, Journal of Biomedical Optics. 20: 126005, 2015. PMID 26677070 Leung NY, Wai CY, Ho MH, Liu R, Lam KS, Wang JJ, Shu SA, Chu KH, Leung PS. Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one-compound peptide libraries. Cell Mol Immunol. 2015 Sep 14. doi: 10.1038/cmi.2015.83. PMID 26364917 Ding Y, Li J, Xiao W, Xiao K, Lee JS, Bhardwaj U, Zhu Z, Digiglio P, Yang G, Lam KS, Pan T. Microfluidic-Enabled Print-to-Screen (P2S) Platform for High-Throughput Screening of Combinatorial Chemotherapy. Anal Chem. 87: 10166-71, 2015 . PMID 26334956. Barisone GA, Satake N, Lewis C, Duong C, Chen C, Lam KS, Nolta J, Diaz E. Loss of MXD3 induces apoptosis of Reh human precursor B acute lymphoblastic leukemia cells. Blood Cells Mol Dis. 54(4):329-35, 2015. PMID: 25554682. Xiao K, Li YP, Wang C, Ahmad S, Vu M, Kuma K, Cheng YQ, Lam KS. Disulfide cross-linked micelles of novel HDAC inhibitor thailandepsin A for the treatment of breast cancer. Biomaterials. 67:183-93, 2015. PMID: 26218744. Liu R, Shih TC, Deng X, Anwar L, Ahadi S, Kumaresan P, Lam KS. Design, synthesis, and application of OB2C combinatorial peptide and peptidomimetic libraries. Methods Mol Biol. 1248:3-22, 2015. Wang WP, Ho PY, Chen QX, Addepalli B, Limbach PA, Li MM, Wu WJ, Jilek JL, Qiu JX, Zhang HJ, Li T, Wun T, White RD, Lam KS, Yu AM. Bioengineering Novel Chimeric microRNA-34a for Prodrug Cancer Therapy: High-Yield Expression and Purification, and Structural and Functional Characterization. J Pharmacol Exp Ther. 354(2):131-41, 2015. Lee C, Carney RP, Hazari S, Smith Z, Knudson A, Robetson C, Lam KS, Wachsmann-Hogiu S. 3D plasmonic nanobowl platform for the study of exosomes in solution. Nanoscale, 7: 9290-9297, 2015. (PMID: 25939587). Fujita M, Zhu K, Fujita CK, Zhao M, Lam KS, Kurth MJ, Takada YK, and Takada Y. Proinflammatory sPLA-IIA induces integrin activation through direct binding to a newly identified binding-site (site 2) in integrins α4β1, and α5β1. J Biol Chem 290: 259-71, 2014. (PMID 25398877). Guo W, Liu R, Bhardwaj G, Yang J, Changou C, Ma AH, Mazloom A, Chintapalli S, Xiao K, Xiao W, Pappanaicken K, Sanzhez E, Yeh CT, Evans C, Patterson R, Lam K., Kung HJ. Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor. Cell Death and Disease, in press, 2014. Ngo T, Barisone GA, Lam KS, Diaz E. MXD3 regulation of DAOY cell profileration dictated by time course of activation. BMC Cell Bio. 15: 30 ( July 23 2014). (PMID 25053245) Li Y, Lin T, Luo Y, Liu Q, Xiao W, Guo W, Lac D, Zhang H, Feng C, Wachsmann-Hogiu S, Walton JH, Cherry SR, Rowland DJ, Kukis D, Pan C, and Lam KS. A Smart and Super Versatile "All-in-One" Theranostic Nanomedicine Platform. Nature Communication, 5: 4712, 2014. (PMID 25158161) Shi C, Yuan D, Nangia S, Xu G, Lam K, Luo J. A Structure-Property Relationship Study of the Well-defined Telodendrimers to improve hemocompatibility of nanocarriers for anticancer drug delivery. Langmuir, 30: 6878-6888, 2014. (PMID 24849780) Zhang H, Li Y, Lin TY, Xiao K, Haddad AS, Henderson PT, Jonas BA, Chen M, Xiao W, Liu R, Lam KS, and Pan CX. Nanomicelle formulation modified the pharmacokinetic profiles and cardiac toxicity of daunorubicin. Nanomedicine (Lond). 2014 Mar 17. (PMID 24628688). Jian Z, Han H, Zhang T, Puglisi JH, Izu L, Shaw JA, Onofiol E, Erickson JR, Chen Y, Horvath B, Shimkunas R, Xiao W, Li Y, Pan T, Chan J, Banyasz T, Tardiff J, Chiamvimonvat N, Bers DM, Lam KS, Chen-Izu C. Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling. Science Signaling 317 (PMID 24643800) Garland SP, Wang RY, Raghunathan VK, Lam KS, Murphy CJ, Russell P, Sun G, Pan T. Photopatternable and photoactive hydrogel for on-demand generation of hydrogen peroxide in cell culture. Biomaterials. 35: 1762-1770. (PMID: 24290809) Li Y, Xiao K, Zhu W, Deng W, Lam KS. Stimuli-response cross-linked micelles for on-demand drug delivery against cancers. Adv Drug Deliv Rev. 66c: 58-73, 2014. (PMID 24060922). Hua S, Saunders M, Dimapasoc L, Jeong SH, Kim S, So M, Lee KS, Jae H, Lam KS, Lebrilla C, An HJ. Differentiation of cancer cell origin and molecular subtype by plasma membrane N-glycan profiling. Journal of Proteome Research, 13: 961-968, 2014. (PMID 24303873) Sun YS, Luo J, Lam KS, Zhu XD. Detection of formation and disintegration of micelles by oblique-incidence reflectivity difference microscopy. Instrument Science and Technology. 41: 545-555, 2013. Xiao K, Suby N, Li Y, and Lam KS. Telodendrimer-based nanocarriers for the treatment of ovarian cancer. Therapeutic Delivery. In press, October 2013. Kenyon NJ, Bratt JM, Lee J, Luo J, Franzi LM, Zeki AA, and Lam KS. Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airway inflammation. PLOS ONE, in press, 2013.