Development of Exosomes based Immuno-Therapy for Cancer
We are developing highly specific bifunctional exosome scavenging agents (ESAs) that facilitate the removal of circulating exosomes at the tumor site by inflammatory phagocytic cells such as neutrophils (white blood cells) and macrophages resulting in the inhibition of tumor progression and metastasis. These bifunctional ESAs will be developed by attaching cancer exosome-specific chemical moeity (exosomes targeting cyclic peptides) to molecules that will recognize and bind to eat me signals (unique receptors) on the surface of phagocytic cells thus, facilitating the circulating tumor exosome removal by host phagocytic cells, very much like bacteria eaten by white blood cells. The cancer types we are currently focusing on include breast cancer, lung cancer and ovarian cancer. The project is highly innovative as the role of ESAs and Cancer growth inhibition has never been explored before. Exosomes derived from tumors are proposed to promote local tumor immune resistance as well as support distal metastasis. This application addresses the novel therapies through the development of ESAs to target tumor-circulating exosomes, prevalent in cancer patients, and remove them with harnessing the body’s immune system to stop tumor progression and metastasis.
Selected Peer Reviewed Publications
- Sumaira Amir, Catalina Simion, Maxine Umeh, Sheryl Krig, Tyler Moss, Kermit L. Carraway III and Colleen Sweeney. Regulation of the T-box transcription factor TBX3 by the tumor suppressor microRNA-206 in breast cancer. Br J Cancer. 2016 May 10;114(10):1125-34.
- Sumaira Amir, Ma AH, Shi XB, Xue L, Kung HJ, Devere White RW. Oncomir miR-125b Suppresses p14(ARF) to Modulate p53-Dependent and p53-Independent Apoptosis in Prostate Cancer. PLoS One. 2013 Apr 9; 8(4)
- Caleb.M. Bailey, Zhila Khalkhali-Ellis, Margaryan N, Seftor, RE, Sumaira Amir, Brian C. Schutte and Hendrix, MJC. Maspin binds directly to interferon regulatory factor 6: Identification of a novel serpin partnership. J Biol Chem. 2005 Oct 7: 280: 34210-7.
- Sumaira Amir, Margarian, NV. Khalkhali, Z, Odero, V.A and Hendrix MJC. Role of maspin as a regulator of uPAR/uPA expression under hypoxia in invasive breast Cancer cells. Cancer Biology ad Therapy 2005 Apr; 4(4): 400-6
- Jirapat Chunthapong, Elisabeth A. Seftor, Zhila Khalkhali-Ellis Richard E.B. Seftor, S. Amir, David M. Lubaroff Paul M. Heidger, Jr. and Mary J.C. Hendrix Dual Roles of E-cadherin in Prostate Cancer Invasion Journal of Cellular Biochemistry. 2004 Feb; 91 (4) 649-661
- Odero-Marah VA, Khalkhali-Ellis Z, Chunthapong J, Amir. S, Seftor RE, Seftor EA, Hendrix MJ. Maspin regulates different signaling pathways for motility and adhesion in aggressive breast cancer cells.Cancer Biol Ther. 2003 Jul-Aug;2(4):398-403
Jiannan Li was born in Xi’an, China, in 1991. He received the B.E. degree in Micro and Nano Electronics from Tsinghua University, China, in 2012, and the M.S. degree in Electrical and Computer Engineering from University of California, Davis, USA, in 2014.
In 2012, he joined Micro-Nano Innovations Laboratory and Lam Lab, University of California, Davis as a Ph.D. student and research assistant. He’s been working on biomedical applications, including peptide synthesis, drug screening, enzymatic analysis, PCR, etc., using microfluidic approaches, especially droplet printing technology. Jiannan was the recipient of the excellence in research award at department of Electrical and Computer Engineering, UC Davis in 2015. His work has been published in peer-reviewed articles such as Analytical Chemistry, Lab on a Chip, etc. Other than research interest, he also likes basketball and beer.
Xiaocen Li (Christine)
Xiaocen Li (Christine) received her B.S degree in Pharmacy and her Ph.D. degree in Medicinal Chemistry in West China School of Pharmacy, Sichuan University, China in 2008 and 2014. After that, she joined Lam Lab in UCDavis as a postdoc. Her research focuses on small molecules modification, peptide, peptoid, PNA, peptide/ peptoid OBOC library design&synthesis, and tumor-targeting drug delivery system discovery. Currently, she is developing novel cancer targeting nano-delivery systems for siRNA and toxins. She also involves in investigating of the high-affinity peptide ligands against immune checkpoint target PD-1 using OBOC combinatorial technology.
- Xinshuai Wang, Li Zhang, Xiaocen Li, Dejiu Kong, Xiaochen Hu, Xuezhen Ding, Junqiang Yang, Mengqi Zhao, Yixuan He, Kit S Lam, Shegan Gao, Tzu-yin Lin*, Yuanpei Li*. Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo. Nanomedicine (Lond). 2018, 13(10):1107-1120.
- Xiangdong Xue, Yee Huang, Xinshuai Wang, Zhongling Wang, Randy P Carney, Xiaocen Li, Ye Yuan, Yixuan He, Tzu-yin Lin, Yuanpei Li*. Self-indicating, fully active pharmaceutical ingredients nanoparticles (FAPIN) for multimodal imaging guided trimodality cancer therapy. Biomaterials. 2018, 161:203-215.
- Qilai Long, Tzu-yin Lin, Yee Huang, Xiaocen Li, Ai-hong Ma, Hongyong Zhang, Randy Carney, Susan Airhart, Kit S Lam, Chong-xian Pan, Yuanpei Li*. Imaging-guided photo-therapeutic nanoporphyrin synergized HSP90 inhibitor in patient-derived xenograft bladder cancer model. Nanomedicine. 2018, 14(3):789-799.
- Tsung-Chieh Shih, Ruiwu Liu, Chun-Te Wu, Xiaocen Li, Wenwu Xiao, Xiaojun Deng, Zsofia Kiss, Ting Wang, Xiaojia Chen, Randy P Carney, Hsing-Jien Kung, Yong Duan, Paramita M Ghosh, Kit S Lam*. Targeting Galectin-1 impairs castration-resistant prostate cancer progression and invasion. Clinical Cancer Research. Clinical Cancer Research. Clincanres. 0157.2018. 2018 Apr 17.
- Yanlei Liu, Fan Yang, Wenwu Xiao, Ruiwu Liu, Hongyong Zhang, Xiaocen Li, Yousif H Ajena, Kit S Lam, Joseph W Leung*. Discovery of specific targeting ligands as the biomarkers for colorectal cancer. Colorectal Cancer. 2017, 6 (4), 121-130.
- Shubing Qiu, Yi Zhao, Sha Liu, Xiaocen Li, Li Guo, Li Hai, Yong Wu*. Design, Synthesis and Evaluation of Dual-targeting Prodrug Co-modified by Organic Amine and L-ascorbic Acid for CNS Delivery. Letters In Drug Design & Discovery, 14 (9), 1065-1072.
- Yuchen Tang, Yann Thillier, Ruiwu Liu, Xiaocen Li, Kit S Lam, Tingjuan Gao*. Single-bead quantification of peptide loading distribution for One-Bead One-Compound library synthesis using confocal Raman spectroscopy. Analytical Chemistry. 2017,89(13),7000-7008.
- Xin-shuai Wang, De-jiu Kong, Tzu-yin Lin, Xiao-cen Li, Yoshihiro Izumiya, Xue-zhen Ding, Li Zhang, Xiao-chen Hu, Jun-qiang Yang, She-gan Gao, Kit S Lam, Yuan-pei Li*. A versatile nanoplatform for synergistic combination therapy to treat human esophageal cancer. Acta Pharmacologica Sinica 2017, 38 (6), 931-942.
- Ruiwu Liu, Xiaocen Li, Kit S. Lam*. Combinatorial chemistry in drug discovery. Current Opinion in Chemical Biology 2017, 38, 117-126.
- Gaurav Bharadwaj, Viet Nhan, ShanChao Yang, Xiaocen Li, Anand Narayanan, Ana Carolina Macarenco, Yu Shi, Darrion Yang, Letícia Salvador Vieira, Wenwu Xiao, Yuanpei Li, Kit S Lam*. Cholic acid-based novel micellar nanoplatform for delivering FDA-approved taxanes. Nanomedicine (Lond). 2017,12(10), 1153-1164.
- Ruiwu Liu, Xiaocen Li, Wenwu Xiao, Kit S. Lam*. Tumor-targeting peptides from combinatorial libraries. Advanced Drug Delivery Reviews, 2017, 110, 13-37.
- Xiaocen Li, Boyi Qu, Xiuxiu Jin, Li Hai*, and Yong Wu*. Design, synthesis and biological evaluation for docetaxel-loaded brain targeting liposome with “lock-in” function. Journal of Drug Targeting, 2014, 22(03), 251-261.
- Xu Cheng1, Xiaocen Li1, Yanjun Duan, Yongguo Yu, Li Hai, Yong Wu*. A new and efficient method for the synthesis of Ulipristal acetate. Steroids, 2014, 84, 78-83.
- Boyi Qu, Xiaocen Li, Mei Guan, Xun Li, Li Hai, Yong Wu*. Design, synthesis and biological evaluation of multivalent glucosides with high affinity as ligands for brain targeting liposomes. European Journal of Medicinal Chemistry, 2014, 72, 110-118.
- Yi He, Xiaolong Li, Jue Li, Xiaocen Li, Li Guo, Li Hai*, Yong Wu*. A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan. Tetrahedron Letters, 2014, 55(29), 3938-3941.
- Yi Zhao, Boyi Qu, Xueying Wu, Xiaocen Li, Qingqing Liu, Xiuxiu Jin, Li Guo, Li Hai*, Yong Wu*. Design, synthesis and biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen with “lock-in” function. European journal of medicinal chemistry, 2014, 82, 314-323.
- MI Jie; LI Xiao-cen; HE Yi; REN Yun; WU Yong*. Improved synthesis of bisoprolol fumarate. Chinese Journal of Medicinal Chemistry, 2014, 1, 23-26. (Chinese)
- Xue-Ying Wu, Xiao-Cen Li, Jie Mi, Jing You, Li Hai*. Design, synthesis and preliminary biological evaluation of brain targeting L-ascorbic acid prodrugs of ibuprofen. Chinese Chemical Letters, 2013, 24, 117-119.
- Xiao-Cen Li, Wei Fan, Li Hai, Shan Qian, Qui-Qi Xiao and Mei Guan*. Design, synthesis and biological evaluation of lipophilic analogs of anethol trithione. Letters in Drug Design & Discovery, 2010, 7, 747-753.
- Guo-Yao Zhang, Shan Qian, Xiao-Cen Li, Yong Wu*. N-(2,5-Dimethoxy-phenyl)-4- nitrobenzene-sulfonamide. Acta. Cryst. E., 2009, E65, 1939.
- Xiaocen Li, Wenwu Xiao, Yayu Wang, Xiaojia Chen, Ruiwu Liu and Kit S. Lam*. α3β1 integrin targeted DM1 micellar prodrug for targeted therapy against ovarian cancer. 2018 American Association of Cancer Research (AACR) Annual Meeting (Chicago, IL 2018.04/14-18, #3731)
- Xiaocen Li, Wenwu Xiao, Yayu Wang, Xiaojia Chen, An Hong, Kit S. Lam* and Ruiwu Liu*. A novel peptide-decorated DM1-conjugated nanotherapeutic agent for targeted therapy against lung cancer. 2017 American Peptide Symposium (Whistler, Canada, 2017.06.17-22, YI- P128)
- Xiao-Cen Li, Jie Mi, Xiu-Xiu Jin, Li Hai, Yong Wu*. Design, synthesis and biological evaluation of glucose-mediated brain-targeting liposome with “lock-in” function. 9th AFMC International Medicinal Chemistry Symposium (AIMCS13 in Taipei, 2013.10.15- 18, P4-02)
- Xiao-Cen Li, Jie Mi, Qing-Qing Liu, Li Hai, Yong Wu*. Design and synthesis of brain targeting l-ascorbic acid prodrugs of ibuprofen with “lock-in” function. 9th AFMC International Medicinal Chemistry Symposium (AIMCS13 in Taipei, 2013.10.15-18, P4-03)
- Boyi Qu, Xiaocen Li, Xun Li, Li Hai, Yong Wu*. Design, synthesis and biological evaluation of multivalent glucosides with high affinity as liposomes ligands for GLUT1. 9th AFMC International Medicinal Chemistry Symposium (AIMCS13 in Taipei, 2013.10.15-18, P4-04)
- Yun Ren, Mei Guan, Ren-Jun Li, Xiao-Cen Li, Li Hai, Yong Wu*. Synthesis and characterization of the major stereoisomers of ezetimibe. 9th AFMC International Medicinal Chemistry Symposium (AIMCS13 in Taipei, 2013.10.15-18, P5-57)
- Renjun Li, Mei Guan, Jianbo Wu, Xiaocen Li, Li Hai, Yong Wu*. Synthesis of 12-(substituted amino) berberrubine derivatives as antidiabetics. 9th AFMC International Medicinal Chemistry Symposium (AIMCS13 in Taipei, 2013.10.15-18, P5-60)
- Shan Qian, Hai-Jiao Li, Xiao-Cen Li, Yong Wu*. Synthesis of oleanolic acid derivatives with modified rings A. 2009 Chinese Medicinal Chemistry Symposium (CMCS2009inWuhan, Abstract. 238)
- Ruiwu Liu, Xiaocen Li, Tsung-Chieh Shih, Joyce S. Lee and Kit S Lam*. Peptide Therapeutics-Oncology. Peptide-based Drug Discovery, Challenges and New Therapeutics 2017, 278-325.
- Yong Wu*, Xiaocen Li, Li Hai. Progress in Carrier-mediated Brain Targeting Drugs. Progress in Medicinal Chemistry 10, Chapter14, Feb 2015, Beijing. (Chinese)
- Kit S. Lam, Xiaocen Li, Ruiwu Liu, Wenwu Xiao. Nanotherapeutic Agent For Cancer Therapy. UC 2018-499-1, 2018-03-13 (a US patent, provisional)
- Yong Wu, Li Hai, Baohou Sun, Yi He, Xiaocen Li. A new method to synthesize rizatriptan benzoate. CN103664900B, 2016-02-24. (a Chinese Patent)
- Yong Wu, Mei Guan, Li Hai, Yingbo Zhao, Yi He, Xiaocen Li. A New Synthesis Method of Rizatriptan Benzoate CN103664901B, 2016-04-13. (a Chinese Patent)
- Yong Wu, Li Hai, Xiaocen Li, Jie Mi, Jing You. Brain targeting prodrugs using Vitamin C as a carrier. CN102989004B, 2014-04-09. (a Chinese Patent)
- Yong Wu, Li Hai, Yongguo Yu, Zheqin Shi, Xiaocen Li. A method for obtaining 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione with high purity. CN102295674B, 2013-04-10. (a Chinese Patent)
- The 3rd poster prize of 23rd Annual Cancer Research Symposium, UC Davis Comprehensive Cancer Center, 09/28/2017
- Prize for Distinguished Graduate Student of Sichuan Province in 2014, 11/2013.
- Prize for Distinguished Graduate Student Cadre of Sichuan University in 2014, 11/2013.
- The 2nd Prize of Kanghong Scholarship, Kanghong Pharmaceutical, Chengdu, 10/2013.
- Graduated student travel rewards, Sichuan University, 07/2013.
- Fuan Scholarship, Fuan Pharmaceutical, Chongqing, 11/2010.
Yuan Sun received B.S degree in Basic Pharmacy (2008) and M.S degree in Medicinal Chemistry (2011) from China Pharmaceutical University, and his Ph.D. in 2016 from The Ohio State University working with Professor Jon Parquette.
Currently, Yuan Sun is a post-doctoral scholar in Dr. Kit S Lam’s lab working on drug delivery and peptide drug discovery. His long-standing interest relies in using modern pharmaceutical science to discover new therapy for cancer treatment.
Outside the lab, Yuan Sun enjoys antique collection, sports as well as hiking.
Samantha is a grad student in Pharmacology and Toxicology program. Her project works on site-specific immunoglobulin conjugation with the linker technology discovered via OBOC screening. Her passion for science goes beyond bench side. From her thesis, she filed a patent and participated at business competition. The team leveraged the research data to formulate a pitch and got second place winner.
Outside of lab, she enjoys outdoor activities, leisure instrument playing and explores different cuisines.
- 2016-2018 American College of Toxicology Fellowship Recipient
- 2016 Big Bang Business Competition Second Place Winner
- 2015-2016 Keller Pathways Business Fellow
- 2016 SOT Biotechnology SS Student Achievement Award Recipient
- Fall 2015 UC Davis GSA Travel Award Recipient
- Lac, D.; Feng, C.; Bhardwaj, G.; Le, H.; Tran, J.; Xing, L.; Fung, G.; Liu, R.; Cheng, R. H.; Lam, K. S. Covalent chemical ligation strategy for monoclonal and polyclonal immunoglobulins at the nucleotide binding sites. Bioconjug Chem 2015
- Lac D, Feng C, Bhardwaj G, Lam KS. Site-Specific Covalent Chemical Ligation to Monoclonal and Polyclonal Immunoglobulin. U.S. Provisional Application #62/144,710
I got my BS in chemistry from Sharif University of Technology in Iran. Then I moved to US in 2014 to obtain my MS degree in organic chemistry from Southern Illinois University-Edwardsville. Currently I am a PhD candidate in UC Davis and working on multiple projects. My main project is development of molecular rotor dye containing sensors for detection of opioids and plasma proteins which requires synthesizing of molecular rotor dye derivatives, preparing OBOC combinatorial peptide libraries, optimizing a novel screening method for such sensors and development of biological assays with these sensors. Some other projects that I have been working on are protein biotinylation quantification using novel illuminating peptide-dye conjugates, genetically encoded small illuminant (GESI) as a novel technology for functional imaging in living cell, etc.
I am mainly interested in organic chemistry with applications in biology and medicine and I believe that life is short, so we must do stuff that matters!
List of Awards and Honors:
- R. Bryan Miller Best Poster Award
Mar 2018-University of California Davis
- GRC Young Investigator Poster Competition (First Prize)
Feb 2018-Gordon Research Conference, Chemistry & Biology of Peptides
- LSAMP STEM Symposium Best Presenter Award
Feb 2016-LSAMP STEM Symposium
- Thomas D. Bouman Memorial Research Scholar Award
Feb 2016- Southern Illinois University Edwardsville
- Academic Achievement Award
Dec 2015-Southern Illinois University Edwardsville
- Erasmus Mundus Scholarship in ASC (Advanced Spectroscopy in Chemistry)
May 2013-Erasmus Mundus
I am interested in natural products synthesis on solid phase beads. I want to make macrocyclic compounds, which are rigid ring structures that may “mimic” natural compounds, such as Tacrilomus for instance. I believe that the human body may recognize natural products better, even if it is a mimetic. Such example is the synthetic drug LSD synthetic mimicking the natural compound Serotonin.
I have worked on Flavonoid scaffold for potentially building combinatorial libraries as well as the “Grubbs” reaction to cyclize LXW64 (Lam lab compound) with an alkene bond. I am working on Coumarin as well. I do computational chemistry also for docking studies and fragment libraries (treating amino acids as “fragments” to increase diversity of libraries). I can also test for good overlap of a native ligand for a protein or even a natural product for better binding and mapping of interacting residues in a protein.
AACR 2018 proceedings Chicago
15th Chinese Peptide Symposium
Growing chili/pepper plants
House work and installations
Watching movies (recent and classics)