Welcome To The Yang Lab
Cancer, the most deadly disease to human health, affects the lives of millions of people globally. cancer, neuronscience, cancer immune Our team is trying to investigate the cause of medulloblastoma, the most common childhood cancer. Aggressive with a tendency to metastasize, medulloblastoma manifests as a range of neurological symptoms. Current therapies are encountering a number of obstacles. Our goal is to identify novel molecular and cellular mechanisms for the development of the most efficient strategies for medulloblastoma treatment.
Research
The Hedgehog (Hh) pathway is a conserved signaling system essential for embryonic development, and any deficiency in this process can lead to birth defects and severe diseases, such as cancer. To understand how Hh signaling regulates embryo development, we are using mouse model and human patient primary culture cell line. Hh pathway promotes cell proliferation, differentiation and migration. Mutations that deregulate Hh signalling have been linked to basal cell carcinoma and medulloblastoma and other diseases, making it of great translational significance. To further investigate this, we are using proteomics and genomics screening to identify important genes and genetic sequences, as well as online databases to uncover important hits for Hh regulation incancers and brain development.
Hedgehog Pathway in embryonic development and cancer
Deficiency in the process of embryo development will lead to birth defect and severe disease, such as cancer. The Hedgehog (Hh) pathway is a conserved signaling system essential for embryonic development. I am interested to understand how Hh signaling regulates embryo development by using mouse/zebrafish model, human patient primary culture cell line, 3D organoid culture. Primary culture cell line is ex vivo cell cultures originating from resected tissues during biopsies and surgeries, research with the use of cell lines is an essential procedure for modelling diseases, stem cell and cancer investigation, and the establishment of therapies. 3D organoid culture models are a more accurate representation of the natural environment experienced. Upon ligand stimulation, Hh pathway promotes cell proliferation, differentiation and migration. However, how the negative regulators modulate signaling during embryo development still remains unknown. Mutations that deregulate Hh signalling have been implicated in basal cell carcinoma and medulloblastoma and of great translational significance. Using CRISPR screening which is used to find a small number of important genes, or genetic sequences, and proteomics approach, online database, revealing several important hits for Hh regulation. Now, we would like to verify those candidates and figure out how those genes impact on Hh pathway.
How Hh pathway regulation in tumor microenvironment
The Hedgehog (Hh) pathway is involved in remodeling the tumor microenvironment (TME), which in turn facilitates tumor progression by modulating the TME's plasticity, immune suppression, and metastasis. Immune-suppressive cells present in the TME include M2 macrophages (TAMs), Treg cells, tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). These cells suppress anti-tumor immune responses by expressing interleukins or producing tumor-promoting cytokines, thus promoting tumor progression. Consequently, we are interested in exploring how the Hh pathway regulates the TME.
Computational modeling in drug development
The Hedgehog (Hh) pathway is a pivotal factor in tumorprogression regulation, and thus, targeting GLI1, the driver of Hh signaling transduction, is the key to resolution. We are also dedicated to developing small chemical compounds as GLI1 inhibitors, to impede the hyperactive Hh signaling transduction. AI-based and computational modelling can be employed for screening and examining the structure of the protein/compounds and protein/ protein interaction, allowing us to gain insight into the molecular mechanisms of diseases and identify potential drug targets.Metabolism regulation in cancer and brain
Metabolism regulation in cancer is a complex process that involves a range of key elements. AMP-activated protein kinase (AMPK) is an integral part of this regulation, as it is responsible for controlling metabolism in both cancer and the brain. We and others have shown that AMPK inhibits Hh signaling and suppresses the growth of medulloblastoma. Moreover, AMPK is essential for energy sensing, neuronal function, and neuroprotection in the brain. Our research focuses on understanding the exact mechanisms andimplications of AMPK signaling in different contexts. Of special attention is the altered metabolism observed in cancer cells, otherwise known as the "Warburg effect" or aerobic glycolysis.
Cell Metabolism ⎹ 2024
Metabolic switch regulates lineage plasticity and induces synthetic lethality in triple-negative breast cancer
YS Zhang*, MJ Wu, WC Lu, YC Li, CJ Chang*, Jer-Yen Yang*
Tumor Microenvironment - New Insights ⎹ 2023
Revealing Hedgehog in Tumor Microenvironment
Xing-Guo Li, Jer-Yen Yang*
Biochemistry and Biophysics Reports ⎹ December, 2022
PRMT1 is an important factor for medulloblastoma cell proliferation and survival
Gu X, He M, Lebedev T, et al., Yang JY and Li XG
Cells ⎹ November, 2021
Hedgehog Pathway Inhibitors against Tumor Microenvironment
S Gampala, JY Yang*
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FASEB BioAdvances ⎹ March, 2021
Activation of AMPK sensitizes medulloblastoma to Vismodegib and overcomes Vismodegib- resistance.
S Gampala, G Zhang, C Chang, JY Yang*
Nature Communications ⎹ September, 2020
TET2 Directs Mammary Luminal Cell Differentiation and Endocrine Response
MR Kim, Y Zhang, MJ Wu, JY Yang*, C Chang*
Oncotarget ┃ May, 2018
Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors
Kumari R, Silic MR, Jones-Hall YL, Nin-Velez A, Yang JY, Mittal SK, Zhang G
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Cell Metabolism ┃ November, 2018
Epithelial-Mesenchymal Transition Directs Stem Cell Polarity via Regulation of Mitofusin
Wu MJ, Chen YS, Kim MR, Chang CC, Gampala S, Zhang Y, Wang Y, Chang CY, Yang JY, Chang CJ
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Handbook of Brain Tumor Chemotherapy ┃ 2018
Chapter title: Targeting the sonic hedgehog pathway in brain cancers: Advances, limitations and future directions
Sherri Y. Huang, Jer-Yen Yang
2017
Scientific Reports ┃ January, 2017
KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors
Cui Z, Shen Y, Chen KH, Mittal SK, Yang JY, Zhang G.
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Oncotarget ┃ July, 2017
Dual degradation signals destruct GLI1: AMPK inhibits GLI1 through β-TrCP-mediated proteasome degradation
Zhang, R., Huang, S.Y., Li, K., Li, YH, Hsu,WH, Zhang G, Chang CJ, and Yang, JY.
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Oncogene ┃ June, 2017
Retinoic acid directs breast cancer cell state changes through regulation of TET2-PKCζ pathway
Wu MJ, Kim MR, Chen YS, Yang JY, Chang CJ.
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Cancer Reports and Reviews ┃ November, 2017
Activation of AMPK inhibits medulloblastoma cell growth and GLI1 activity
Huang, SY., Chen, SK and Yang JY.
2016
Plos One┃ September, 2016
Molecular evolution of MDM1, a “Duplication-Resistant” Gene in Vertebrates
Hensley, MR, Chua RF., Leung YF, Yang, JY, Zhang, G
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Environ Sci Technol┃ July, 2016
Chlorine/UV Process for Decomposition and Detoxification of Microcystin-LR
Zhang X, Li J, Yang JY, Wood KV, Rothwell AP, Li W, Blatchley Iii ER
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Scientific Report ┃ June, 2016
Evolutionary and developmental analysis reveals KANK genes were co-opted for vertebrate vascular development
Hensley MR, Cui Z, Chua RF, Simpson S, Shammas NL, Yang JY, Leung YF, ZhangG
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Neurooncology┃ 2016
Medulloblastoma: Clinical Challenges and Emerging Molecular Discoveries
Eric Q. Trieu, Sherri Y. Huang, Jer-Yen Yang
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Recent Advances in Brain Tumor┃ 2016
Targeting Medulloblastoma: Genetic and Metabolic Signatures in the Focus
Rui Zhang, Sherri Y. Huang, Jer-Yen Yang
2015
Cancers ┃ December, 2015
Targeting the Hedgehog Pathway in Pediatric Medulloblastoma.
Huang, S.Y.; Yang, JY
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Cell Reports ┃ July, 2015
AMP-activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma.
Li YH, Luo J, Mosley YY, Hedrick VE, Paul LN, Chang J, Zhang G, Wang YK, Banko MR, Brunet A, Kuang S, Wu JL, Chang CJ, Scott MP, Yang JY*.
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Cancer Research ┃ June, 2015
Leptin-STAT3-G9a signaling promotes obesity-mediated breast cancer progression.
Chang CC, Wu MJ, Yang JY, Carmarillo I, Chang CJ.
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Int Rev Cell Mol Biol ┃ November, 2015
New insight into cancer aneuploidy in zebrafish.
Zhang G, Yang JY, Cui Z.
2014
Cancer Research ┃ December, 2014
A H3K9 Methyltransferase, KMT1E, Suppresses Lung Cancer Cell Metastasis Through the SMAD2/3 Pathway.
Wu PC, Lu JW, Yang JY, Lin IH, Ou DL, Lin YH, Chou KH, Huang WF, Wang WP, Huang YL, Hsu C, Lin LI, Lin YM, Shen CK, Tzeng TY.
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J Clin Invest ┃ October, 2014
Dysregulated miR-205 signaling promotes symmetric division of self-renewing mammary stem cells and mammary tumorigenesis.
Chao CH, Chang CC, Wu MJ, KO HW, Wang D, Hung MC, Yang JY, Chang CJ.
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Applied & Translational Genomics ┃ December, 2013
Phylooncogenomics: Examining the cancer genome in the context of vertebrate evolution.
Zhang GJ, Vemulapalli TH, Yang JY
2011~(selected papers)
Nature Cell Biology ┃ January, 2011
CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells.
Wei Y, Chen YH, Li LY, Lang J, Yeh SP, Shi B, Yang CC, Yang JY, Lin CY, Lai CC, Hung MC.
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Cancer Cell ┃ January, 2011
EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-b-catenin signaling.
Chang CJ, Yang JY, Xia W, Chen CT, Xie X, Chao CH, Woodward WA, Hsu JM, Hortobagyi GN, Hung MC.
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Nature Cell Biology ┃ March, 2011
p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs.
Chang CJ*, Chao CH*, Xia W, Yang JY, Xiong Y, Li CW, Yu WH, Rehman SK, Hsu JL, Lee HH, Liu M, Chen CT, Yu D, Hung MC.
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J Clin Invest ┃ November, 2011
APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis.
Ding Q, Chang CJ, Xie X, Xia W, Yang JY, Wang SC, Wang Y, Xia J, Chen L, Cai C, Li H, Yen CJ, Kuo HP, Lee DF, Lang J, Huo L, Cheng X, Chen YJ, Li CW, Jeng LB, Hsu JL, Li LY, Tan A, Curley SA, Ellis LM, Dubois RN, Hung MC.
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Current Drug Targets ┃ March, 2011
Deciphering and targeting Forkhead Transcriptional Factors in Cancer Therapy. 28. (Invited review)
Yang JY and Hung MC
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Cancer Research ┃ June, 2011
Activation of FOXO3a is sufficient to reverse mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor chemoresistance in human cancer.
Yang JY, Chang CJ, Xia W, Wang Y, Wong KK, Engelman JA, Du Y, Andreeff M, Hortobagyi GN, Hung MC.
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Clinical Cancer Research ┃ February, 2009
A new fork for clinical application: targeting forkhead transcription factors in cancer.
Yang JY, Hung MC.
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Nature Cell Biology ┃ February, 2008
ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation.
Yang JY, Zong CS, Xia W, Yamaguchi H, Ding Q, Xie X, Tsai CH, Sahin AA, Muller WJ, Mills GB, Yu D, Hortobagyi GN, Hung MC et al.
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Cancer Research ┃ August, 2008
Down-regulation of myeloid cell leukemia-1 through inhibiting Erk/Pin 1 pathway by sorafenib facilitates chemosensitization in breast cancer.
Yang JY, Ding Q, Huo L, Xia W, Wei Y, Liao Y, Chang CJ, Yang Y, Lai CC, Lee DF, Yen CJ, Chen YJ, Hsu JM, Kuo HP, Lin CY, Tsai FJ, Li LY, Tsai CH, Hung MC.
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Cell ┃ August, 2007
IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway.
Lee DF, Kuo HP, Chen CT, Hsu JM, Chou CK, Wei Y, Sun HL, Li LY, Ping B, Huang WC, He X, Hung JY, Lai CC, Ding Q, Su JL, Yang JY, Sahin AA, Hortobagyi GN, Tsai FJ, Tsai CH, Hung MC.
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Int J Oncol ┃ September, 2006
Ionizing radiation activates expression of FOXO3a, Fas ligand, and Bim, and induces cell apoptosis.
Yang JY, Xia W, Hu MC.
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Molecular & Cellular Biology┃ October, 2006
MDM2 promotes cell motility and invasiveness by regulating E-cadherin degradation.
Yang JY, Zong CS, Xia W, Wei Y, Ali-Seyed M, Li Z, Broglio K, Berry DA, Hung MC.
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Molecular Cell ┃ July, 2005
Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin.
Ding Q, Xia W, Liu JC, Yang JY, Lee DF, Xia J, Bartholomeusz G, Li Y, Pan Y, Li Z, Bargou RC, Qin J, Lai CC, Tsai FJ, Tsai CH, Hung MC.
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Cell ┃ April, 2004
IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a.
Hu MC, Lee DF, Xia W, Golfman LS, Ou-Yang F, Yang JY, Zou Y, Bao S, Hanada N, Saso H, Kobayashi R, Hung MC.
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Cancer Research ┃ December, 2004
Adenoviral E1A targets Mdm4 to stabilize tumor suppressor.
Li Z, Day CP, Yang JY, Tsai WB, Lozano G, Shih HM, Hung MC.
Who We Are
Jer-Yen Yang Ph.D.
Associate Professor of Cancer and Developmental Biology
PI
Dr. Yang got his PhD from UT MD Cancer Center, studied EGFR signaling in breast and lung cancer. He then joined Stanford University to study the Hh pathway in medulloblastoma and brain development. As a PI at Purdue University and Roswell Park Cancer Center, his lab focuses on how Hh signaling and metabolism control MB and neuron growth. In Aug 2020, he relocated his lab to CMU, Taiwan, continuing cancer immuno-metabolism and Hh signaling research. Dr. Yang enjoys hiking, photography, Ping Pong, basketball, and meditation.
Wan-Chi Lu (Amy)
Research assistant
I joined Dr. Yang’s lab at 2021. And I received my B.S. at China Medical University, on Development of Biological Science and Technology. I am currently pursuing my master degree on Biochemistry and Molecular Biology, working on hedgehog pathway and cancer neuro-regulation.
Sophie Chen
Master student (Biomedical Science major)
Hello,I’m Sophie Chen. I’m a master’s student of Biomedical sciences. It’s mypleasure to join Professor Yang’s lab, which I’m really interest in the topicof cancer. Hopefully, during these two years, I could learn the theory ofcancer and the techniques to conduct cancer researches. As the saying goes, Knowledge is power, which I can’t agree with it anymore. Thank you for viewing my self-introduction.
Kawsar Ahmed (Visiting Ph.D student)
This is Mr. KAWSAR AHMED from Bangladesh. I’m an overseas doctoral candidate at Central South University, China. My Ph.D. major is in Applied Statistics. My current research area is on statistical learning; particularly causal inference estimation approaches for observed and unobserved data such as to study heterogeneity, treatment effects in RCTs or observational data, causal survival analysis, and longitudinal study. However, I’m delighted to be connected with Professor Yang’s lab at China Medical University, where we can foster an innovative learning environment for research work.
Hannah Yang
Undergraduate Student (Life science major)
I am studying in the Department of Biotechnology at China Medical University. I was interested in experimental content when I was a sophomore, so I joined Yang Lab. Thought the guidance of Professor Yang, I learned more academic content and experimental techniques, and improved my ability. It’s a great honor to be a student of Yang lab.
Claire Lin
Undergraduate Student (Medicine major)
My name is Claire! I major in medical, and I’m a freshman. English is a hobby to me, and I like to read any English literature, including papers and books. Also, I love animals. I keep regular ones such as cats, dogs, birds and fish, but there are also chickens, ducks, geese in my yard. I am interested in conducting experiments and researches, and I’m very happy to join this lab.
News in The Yang Lab
July 2024
- Congratulations to Wan-Chi Lu (Amy) for successfully defending her master’s thesis!
April 2022
- Cathy and Ibrahim award the oral presentation with cash awards!
September 2020
- A New Treatment Direction for Drug-resistant Breast Cancer! CMU Research Team Published Their Findings in Nature Communications.
August 2020
- We will move to a new research building in Taichung in Dec, 2020. Looking for self-driven and highly motivated RAs, graduate students and postdocs who are interested in cancer and developmental biology.
- Our Tet2 paper is accepted by Nat Comm.
Contact Us
Jer-Yen Yang, Ph.D.
Associate Professor of Cancer and Developmental Biology
Graduate Institute of Biomedical Sciences
China Medical University, TaiwanInstitute of Biochemistry and Molecular Biology
E-mail: jyyang@cmu.edu.tw
Office: +886-4-2205-3366 #6715
Lab: +886-4-2205-3366 #6707
Address: No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City 406040, Taiwan
13F, Excellence BuildingWe are seeking for postdoctoral researcher and graduate student to work on Hedgehog pathway and metabolism regulation in developmental biology and cancer research. We study signal transduction and molecular/cellular regulations using cellular, mouse model in cancer and neuronal research.
Postdoctoral researcher candidates with Ph.D. degree, a strong background in molecular and cell biology and/or mouse genetics, and highly motivated for conducting cutting-edge research are welcome to apply. For graduate students and research assistants who have cellular and molecular biology background and interested in cancer and developmental biology.
To apply, please send a CV, a brief description of research experiences and interests, and three letters of reference to jyyang@cmu.edu.tw
Undergraduate students who are interested in biomedical science and cancer biology are welcome to apply.楊哲彥老師實驗室
實驗室簡介
實驗室主要在研究癌症、代謝及小腦的發育,我們利用細胞及動物模式來研究腦癌及乳癌的癌化過程及其抗藥性,結合系統生物學及大數據演算來尋找最重要的致癌基因並了解其致病機轉,藉此尋求有效的治療方法來進行臨床研究。
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研究主題
1. 髓母細胞瘤 (Medulloblastoma, MB) 中的刺蝟信號 (Hedgehog (Hh) signaling)
髓母細胞瘤好發於18歲以下的小孩,尤其嬰幼兒。目前已知約30%的病患具有Hh Pathway異常表達的情況,在治療上仍然以傳統手術、放療及化療為主流,近期免疫療法正在研究中。我們實驗室目標在於研究更有效的標靶藥物來治療該疾病及臨床上已產生的抗藥性問題。
2. Hh pathway對腫瘤微環境的調控
現已知能透過調控腫瘤微環境(TME)的可塑性、免疫抑制、腫瘤轉移…等方式使腫瘤惡化,而其中Hh pathway被認為在重塑TME中是重要的信息傳遞機轉。腫瘤藉由活化Hh pathway使TME中的各類細胞展現有助於腫瘤惡化的性狀,例如分泌抑制免疫的白血球介素(interleukin)、促進腫瘤生長的細胞因子(cyotkines)、抑或是促進上皮细胞间质化(EMT)。因此我們的研究目標是要找出Hh pathway以及其他胚胎發育訊號路徑調控腫瘤為環境的機轉。
3. GLI1 拮抗藥物研發
如前所述,Hh pathway是調控腫瘤惡化中很重要的訊號路徑。因此,我們以該路徑中最重要的標的,GLI1蛋白為目標研發小分子化合物的GLI1拮抗劑,以截斷在腫瘤中過度活躍的Hh pathway.
4. 代謝調控因子AMPK如何控制髓母細胞瘤
腦組織在能量代謝的需求上是很敏感的,特別是在腦癌方面,我們實驗室已發表數篇論文證實主要的能量代謝調控因子AMPK會控制Hh Pathway且抑制Hh的分子機理,並證實應用AMPK活化劑可以有效抑制MB細胞生長,為該疾病提供一個新型有效療法 (詳情請參閱Publication)。———————————————————————————————————————————————————
實驗室位置
位於中國醫藥大學校本部 (水湳校區) 的卓越大樓13F,老師於2020年8月從美國返台,目前實驗室仍有空間及經費來增聘有志科研的青年朋友、研究生或助理數名,另外博後具備癌症生物醫學專長且有動物研究專長亦歡迎來信申請,請檢附個人履歷、研究主題及三位推薦人電郵至jyyang@cmu.edu.tw。
Alumni
- Vibha Taneja (2022) Postdoc
- Cathey Liu (2022) Undergraduate Student
- Yiran Lin (2022) High School Student
- Brian Lin (2022) High School Student
- Rui Zhang (2017) Postdoc
- Huong (Kelly) Pham (2016) Summer intern, Undergraduate student
- Yen-Hsing Li (2015) Postdoc
- Justine Gullaba (2014) PVM summer student
- Yung-Yi Mosely PhD (2013) Postdoc
- Chih-Yu Chen (2013) Visiting PhD student
- Emily Liu (2012) Summer intern, High-school student
- Stephanie Liu (2012) Summer intern, High-school student