Lab Members

Dr. Markus Müschen is the Arthur H. and Isabel Bunker Professor of Hematology, HHMI Faculty Scholar and was appointed Director of the Center of Molecular and Cellular Oncology at Yale in October 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.

I graduated from the University of Milan with a bachelor's degree in Biological Science in 2019, and with a master's degree in Biology applied to biomedical research (Summa Cum Laude) in 2021. During my master's degree, I worked in Dr. Manzo’s Lab at the European Institute of Oncology in Milan where we were able to improve the Adoptive T Cell Therapy in melanoma-bearing mice. Thanks to this beautiful experience I decided to continue doing research, and this prompted me to apply for a position in Dr. Müschen’s Lab.

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.

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.

David graduated from Universidad Autónoma de Centro América with a B.A. in Medical Sciences (Summa Cum Laude) and finished the MD curriculum in Costa Rica. Currently, he works at the Müschen laboratory helping develop a model of B cell maturation.

Dr. Franz Ketzer received his BSc in Nutritional Sciences at Friedrich-Schiller-University Jena, Germany in 2016. He conducted his thesis on the effect of aluminum-nanoparticles on colon cancer cells supervised by Prof. Dr. Michael Glei, sparking his interest in cancer research. In 2018, he proceeded to complete the MSc curriculum in Molecular Medicine in Ulm, Germany, specializing in Molecular Oncology. During his MSc thesis, he studied the role of BLNK in the regulation of FOXO1 in B-cell acute lymphoblastic leukemia, supervised by Prof. Dr. Thomas Wirth and Dr. Alexey Ushmorov at the Institute of Physiological Chemistry. As part of the International Graduate School for Molecular Medicine Ulm (IGradU), he subsequently completed his PhD work in the same group but shifted his focus to the role of CCND3 in the maintenance of B-cell acute lymphoblastic leukemia. In 2022, he received his PhD (magna cum laude) in Molecular Medicine, after publishing his findings on the essential, anti-apoptotic role of CCND3 outside of its functions within the cell cycle in B- cell acute lymphoblastic leukemia. In June 2022, he joined the Müschen laboratory at Yale as a postdoctoral associate, with a focus on signaling molecules downstream of the B-cell-/T-cell receptor in the etiology of hematopoietic malignancies and autoimmune disease.

Dhruv graduated with a BSc in Biotechnology & Business from the University of Waterloo in Canada. As part of the Müschen lab, he is focused on developing his knowledge and skills in the area of cancer biology, whilst applying his business knowledge in the development and commercialization of potential therapeutics. Outside of the lab, Dhruv enjoys running outdoors and playing the guitar.

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.

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.

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.

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.

Dr. Qin Li completed her PhD in cellular immunology in 2012 from Sun Yat-sen University Zhongshan School of Medicine. After a postdoctoral training at Yale University School of Medicine in Dr. Naftali Kaminski’s lab, she joined Dr. Markus Müschen’s laboratory from April 2022. Her PhD training is focusing on antigen specific CD4+T cell mediated immune response against Mycobacterium infection and postdoc training is focusing on B cell pathology in pulmonary fibrosis and identification of biomarkers in peripheral blood. Her research interest is in T/ B cell biology in human diseases, especially autoimmune diseases, and hematology cancer.

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.

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.

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.

Andrew graduated from the University of California, Los Angeles with a BS in Microbiology, Immunology, and Molecular Genetics. He first arrived at Yale as a postgraduate associate with Dr. Carrie Lucas studying PI3K signaling in primary immunodeficiencies and is now an Immunobiology graduate student in the Müschen lab.

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”.

Dr. Zhang received his PhD in Biochemistry and Molecular Biology in 2020 from Shanghai Institute for Biological Science, Chinese Academy of Science(CAS) and then joined Institute of Neuroscience of CAS to start his postdoctoral training in YANG HUI lab. His PhD training is focusing on liver cancer and postdoctoral training is focusing on CRISPR tools for disease therapy. From January 2022, Chang joined Müschen lab and decided to employ mouse genetics and the use of genome editing tools (CRISPR-Cas9) towards the development of pre-clinical models to investigate the mechanisms of B-cell development and leukemogenesis.