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Lab Members

  • Arthur H. and Isabel Bunker Professor of Medicine (Hematology) and Professor of Immunobiology; Director, Center of Molecular and Cellular Oncology

    Dr. Markus Müschen is the Arthur H. and Isabel Bunker Professor of Medicine (Hematology) and was appointed Director of the CMCO in 2020. He obtained his MD degree in Biochemistry with Helmut Sies (summa cum laude) from the Heinrich-Heine-Universität in Düsseldorf, completed his residency in Hematology-Oncology with Volker Diehl and his MD-PhD with Martin Krönke in Immunology at the University of Cologne, Germany. Since 2009, the Müschen laboratory has established new conceptual frameworks for the understanding of B-cell signaling and energy metabolism and how defects in these mechanisms contribute to autoimmunity and B-cell transformation. Influenced by his postdoctoral training in basic immunology (Klaus Rajewsky and Ralf Küppers) and cancer genetics (Janet D. Rowley), Dr. Müschen is particularly interested in signal transduction pathways that change the clinical trajectory of human B-cell malignancies and B-cell driven autoimmune diseases. 

  • Research Scientist, Internal Medicine (Hematology)

    Dr. Lai (Linda) Chan completed her PhD with Dr. Fuyuhiko Tamanoi at the University of California Los Angeles where she applied a chemical biology approach to study lipid posttranslational modifications of RAS family of small G-proteins in solid tumors. For her postdoctoral training, she joined Dr. Markus Müschen’s laboratory at Children’s Hospital Los Angeles and later at the University of California San Francisco to investigate mechanisms that drive disease progression and therapeutic responses in B-cell malignancies. Throughout her career, she has used multi-disciplinary approaches (e.g. immunology, hematology/oncology, cancer genetics, cell and molecule biology, biochemistry, chemical biology, CRISPR gene editing and single-cell analyses) and leveraged strategic collaborations to pursue both basic and preclinical translational cancer research.  

  • Associate Research Scientist

    Dr. Kadriye Nehir Cosgun received her Ph.D degree in Stem Cell Biology in 2013 from Technical University of Dresden, Germany. Her PhD thesis titled “Kit regulates HSC engraftment across mouse human species barrier.” was supervised by Prof. Dr. Claudia Waskow and awarded with “The Best PhD thesis in 2013” by Center Regenerative Therapies Dresden. For her post-doctoral training she joined the laboratory of Prof. Dr. Markus Müschen at University of California, San Francisco and later at City of Comprehensive Cancer Center, Los Angeles. Dr. Cosgun is interested in Wnt/beta-catenin signaling in B cell malignancies and the role of pre-BCR signaling in  B-cell leukemia.

  • Postgraduate Associate

    Matthew graduated from Yale College ('21) with a B.S. degree in Molecular Biophysics and Biochemistry. While an undergraduate, he interned at the Bamford lab and Holley lab working on computational biology, bioinformatics, and electrophysiology. Currently, he works as a postgraduate associate at the Muschen lab on applying machine learning to analyze biological datasets in cancer genetics.

  • Research Associate

    Lars Klemm obtained his B.Sc. from the Heinrich-Heine-Universität Düsseldorf, Germany and subsequently got his M.Sc. from the same university in 2009. He has been the Laboratory Manager for the Müschen Lab since 2006. Lars is responsible for keeping the Müschen Lab operational, assisting the team with their experiments and finding/researching new technologies that can be applied to our studies.

  • Associate Research Scientist

    Dr. Kohei Kume completed his PhD at Iwate University (Morioka, Japan) in 2011 with mentorship from Yasushi Saitoh, PhD. After a postdoctoral training at Iwate Medical University with mentorship from Satoshi S. Nishizuka MD, PhD, he joined Dr. Markus Müschen’s laboratory in 2017 at the Beckman Research Institute of the City of Hope. He is currently an Associate Research Scientist in Dr. Müschen’s laboratory at Yale University, and studies the mechanisms and functional significance of autonomous Ca2+ oscillations in oncogenic signaling of multiple B-cell malignancies.

  • Research Scientist, Internal Medicine (Hematology)

    My research interest lies mainly in discovering the novel molecular target to treat B cell leukemia and lymphoma. To do that, our lab leverages genetic engineered mouse model to study the role of gene of interests in 1) B cell development, 2) BCR-mediated immune response and 3) leukemogenesis.

  • Hospital Resident

    Etienne Leveille is a resident physician in the hematology & oncology branch of the ABIM Physician-Scientist Research Pathway at the Yale School of Medicine. He completed his medical school at McGill University, where he also studied the genetics of Parkinson’s disease and hereditary spastic paraplegia under the supervision of Dr. Ziv Gan-Or and mechanisms of inhibition of apoptosis in diffuse large B-cell lymphoma with Dr. Nathalie Johnson. While at McGill , Etienne was also the Co-Editor-in-Chief of the McGill Journal of Medicine. In addition to his clinical work as a resident, Etienne is a member of the Center of Molecular and Cellular Oncology and studies B-cell dynamics and oncogenic signaling in B-cell malignancies under the mentorship of Dr. Markus Müschen. 

     

     

     

     

  • Associate Research Scientist; Program Manager, Center of Molecular and Cellular Oncology

    Aline graduated from the University of Sao Paulo in Brazil with a B.Sc. in Biological Sciences in 1994. She went on to pursue an M.Sc. and a Ph.D. in Aquatic Biology at the National Institute of Amazonian Research with a focus on Fish Physiology and Environmental Toxicology. During her postdoctoral training at the University of Notre Dame and the University of California Riverside in 2005 and 2006, respectively, she continued to work on aquatic contaminants and their effects on fish using molecular and biochemical markers. Following her postdoctoral studies, she engaged in administration, operations, and research support at academic institutions such as the Beckman Research Institute of the City of Hope and the University of California Los Angeles. She joined Yale University as the Program Manager for the Center of Molecular and Cellular Oncology in 2020.

  • Clinical Fellow

    Sayeef is a clinical fellow in Hematology/Oncology at the Yale School of Medicine. 

    He completed both BS/MD and BS/MPH accelerated tracks at the University of South Florida where he stayed for residency in internal medicine rotating through Tampa General Hospital, James A Haley VA Hospital, and Moffitt Cancer Center. During his chief residency, he served as the Director of Resident Research and served as an academic attending. He also completed coursework in the cancer biology PhD program at Moffitt Cancer Center where he advanced his research interests in transplant and cellular therapies. 

  • Postdoctoral Associate

    During my PhD at Cardiff University I developed novel bioinformatics methods to analyze nucleosome maps generated by MNase-digest sequencing in order to understand the roles of chromatin remodelers in controlling developmental expression programs through nucleosome positioning. Following my PhD I moved to the lab of Dr. Niklas Feldhahn at Imperial College London where I first became interested in hematological oncology research. Our work mapping DNA-damage and enhancer reprogramming in transformed B-cells helped to explain why lineage specific markers recurrently mutated in B-cell acute lymphoblastic leukemia (B-ALL). I also performed topology mapping to identify oncogenic enhancer co-option, uncovering the mechanisms of MECOM expression and function underlying the dismal prognosis of this subset of acute myeloid leukemia patients. To further my interest in computational hematology-oncology I joined the lab of Dr. Markus Müschen in 2019 working alongside bench scientists to identify novel therapeutic vulnerabilities of B-cell malignancies. Through integrative analysis of clinical, transcriptional, proteomic and phosphoproteomics data in B-ALL and mantle cell lymphoma (MCL) models I helped uncover an unexpected mechanism of lipid-raft formation leading to PI3K amplification loop downstream of the B-cell receptor. Working alongside Dr. Lai Chan, my identification of mutational segregation between patient cohorts with STAT5- and ERK-pathway driven B-ALL helped lead to the development of a concept of oncogene convergence. This work showed that convergence on a single oncogenic driver was essential for development of B-ALL, and that activation of divergent pathways subverts oncogenesis. This convergence theory gives rise to the exciting possibility of combining divergent pathway activation synergistically with principal driver inhibition as a novel therapeutic strategy. By extending this analysis to study all major oncogenic pathways pan-cancer I now aim to identify whether oncogenic convergence is unique to B-ALL, or whether it represents a new hallmark of cancer that can be exploited to design personalized combination therapies.

  • Postgraduate Associate

    Graduated from the University of Virginia in 2021 with a B.A in cognitive science and a concentration in computer science. During the course of my studies, I was an undergraduate research assistant in Dr. Anindya Dutta's lab under the Biochemistry and Molecular Genetics department of UVA's School of Medicine. Among a few other things, I helped develop an RShiny web-application that will serve as a screening tool to help discover novel genes that affect small-RNA targeting. 

  • Graduate Student, Immunobiology Graduate Program

    Ruifeng graduated from Xiamen University in 2020 with a B.S. degree in Biological Sciences. In the sophomore summer, he had his first research experience in autophagy. He then joined an immunology lab studying B cell central tolerance at Xiamen University. His interest in hematological malignancy was piqued when he did his graduation project at Yale in Dr. Joao Pereira's lab, where he studied how B-ALL impacted B lymphopoiesis. Outside the lab, Ruifeng enjoys swimming, cooking and watching anime.

  • Postdoctoral Fellow

    After I finished my training as a Mathematician/Computer Scientist (B.Sc. and M.Sc.), I went on to pursue a medical degree at the Technical University of Munich (TUM). In parallel, I also started work on a research project in the lab of Dr. Jürgen Ruland in the Institute for Clinical Chemistry at the university hospital Klinikum Rechts der Isar within the Ph.D. program "Medical Life Science and Technology". I finished the program in 2020 and worked in the Ruland Lab as a clinician-scientist postdoctoral fellow until March 31, 2021. Within my Ph.D. project “Analysis of tumor evolution in a model of T-NHL”, I developed a transgenic mouse model, which allows for acute activation of oncogenically enforced T cell receptor pathways conditionally in CD4+ T cells in vivo. This model was based on a knock-in mouse, which had been generated previously in our laboratory and which harbors the human T cell Non-Hodgkin lymphoma (T-NHL) derived ITK-SYK fusion kinase in the Rosa26 locus (K Pechloff et al. “The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma.“ JEM. 2010; 207(5):1031-44). I observed that the single expression of ITK-SYK in mature CD4+ T cells is sufficient to trigger a massive expansion of these cells. However, this proliferation is only transient and insufficient to drive lymphomas. To identify suppressive pathways, which counteract the full transformation of the oncogene sensitized T cells, I performed an in vivo screen using transposon mutagenesis with the help of the laboratory of Dr. Roland Rad. I discovered that a disruption of the PDCD1 gene, which encodes for the PD1 checkpoint receptor, is sufficient for immediate, full transformation of ITK-SYK driven T cells into aggressive lymphomas which resembled molecular, pathological, and clinical features of the human disease. Along with a bioinformatician from our institute, Dr. Christof Winter, we performed a bioinformatic reevaluation of published human data sets from T-NHL patients and found genomic PDCD1 gene alterations in 23% of all investigated cases. For this analysis, it was very helpful that I had been trained in Mathematics and Computer Science before starting biomedical research. In the murine model, the targeted deletion of only one PDCD1 allele was already sufficient to permit lymphomagenesis, establishing together that PD1 functions as a haploinsufficient tumor suppressor in T-NHL. The PD1 pathway receives high attention in immuno-oncology because it can trigger the dysfunctionality of T cells in suppressive tumor microenvironments. Clinically approved antibodies either directed against the PD-1 receptor or against the ligand PD-L1 can block PD- 1 signaling in cancer patients and enhance T cell-mediated anti-tumor immunity. Based on highly successful clinical results in multiple tumor entities, checkpoint Inhibitors are also currently explored for lymphoid cancers including T-NHLs. However, in T-NHL, the tumor cell is a T cell itself and since PDCD1 acts as a tumor suppressor gene in these malignancies, I explored the consequences of anti-PD-1 or anti-PD-L1 checkpoint inhibition in our transgenic mouse model. Consistent with the genetic inactivation, I found that checkpoint inhibitor treatment massively accelerated the expansion of ITK-SYK expressing lymphomatous T cells leading to fatal organ infiltrations within days. Our results demonstrated that pharmacological interference with PD-1 signaling by checkpoint inhibitors can, in principle, accelerate malignant T cell growth (T Wartewig et al. "PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis". Nature 2017; 552:121-125). Indeed, subsequent results from a clinical phase II trial demonstrated the relevance of this hypothesis for T-NHL patients (L Ratner et al. “Rapid Progression of Adult T-Cell Leukemia-Lymphoma after PD-1 Inhibitor Therapy.” N Engl J Med. 2018; 378(20): 1947-1948). The authors documented the potentially devastating effects of checkpoint inhibitor treatment in T-NHL patients, which we had proposed earlier based on my findings. Dr. Ruland and I summarized these and additional consequences from our study, mechanistic implications, and open questions in the review article “PD-1 Tumor Suppressor Signaling in T Cell Lymphomas.” Additionally, I contributed with bioinformatic analysis of the B cell receptor repertoire and RNAseq analysis on two other publications, “Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells” and “The uric acid crystal receptor Clec12A potentiates type I interferon responses”.

  • Postgraduate Associate

    Tony graduated from the University of British Columbia with a master's degree in Data Science. His involvement at the intersection of healthcare and technology — with an emphasis in machine learning — has led to research collaborations on explainable artificial intelligence; genomics; clinical trials in transcatheter aortic valve replacement (TAVR), spontaneous coronary artery dissection (SCAD), and women's heart health; and novel combination cancer therapies.

    Additionally, Tony trained as a classical pianist under the mentorship of Arnaldo Cohen and Emile Naoumoff at the Indiana University Jacobs School of Music. He was a Fellow at the Banff Centre for Arts & Creativity and Orford Music, where he worked with Yoheved Kaplinsky, Dang Thai Son, and André Laplante, among others.