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CRB Newsletter 2023

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2023

ADVANCING OUR HORIZONS The Future is Bright at CRB


Welcome

A message from the chair...

Dr. Deneen Wellik, PhD

It has been an eventful 2023 and the Department of Cell and Regenerative Biology (CRB) has much to celebrate and to remember this year. During the 2023 calendar year, we very happily welcomed four new senior (Full Professor) faculty to our ranks. In February, Jeff Dilworth and Marjorie Brand joined us to continue their remarkable career in Madison, joining the main departmental research space on the 4th floor of WIMR II. After several years on faculty at the Stem Cell Institute at the Ottawa Health Research Institute and the University of Ottawa, we were able to convince them to bring their research programs to CRB. Dr. Dilworth will continue his work dissecting the genetic and epigenetic regulation of muscle stem cells. Dr. Brand was successfully recruited to CRB and the Wisconsin Blood Cancer Research Institute (WBCRI, more on this later!) where she maintains robust research in both regulatory mechanisms of erythropoiesis and how mis-regulation of blood differentiation pathways lead to leukemia. After participating on faculty at UW-Madison for several years in the Surgery Department, Dr. Bo Liu moved her appointment and active research program in vascular biology to CRB this past summer. She and her laboratory moved into CRB space and Dr. Liu also took on a new role at the School of Medicine and Public Health Interdisciplinary Clinical and Translational Research (ICTR) program as Co-Director of the Institutional Career Development KL2 Program. In November, we welcomed Dr. Jeremy Nance to CRB. Dr. Nance was jointly recruited by CRB and by the Center for Quantitative Cell Imaging/Institute (CQCI). He moved his

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laboratory to CQCI in the Bock Laboratories in November where he is re-establishing his strong research program in mechanisms of early organogenesis of C. elegans using advanced imaging techniques. The recruitment of these four strong senior investigators has provided outstanding balance in our relatively new department, adding to the very strong programs led by junior faculty who were recruited in the past several years (Drs. Blum, Colman and Bhattacharyya, who have already been promoted to Associate Professors with tenure, and Drs. Kang, Mahmoud, Tamplin, Lo Sardo and Ponik, all currently at the Assistant Professor rank). Please see more information on the programs of Drs. Dilworth, Brand, Liu and Nance on page 5. With these new hires and continued growth of research activity in CRB, we noted the quadrupling of FTEs in the CRB research space over the past 5 years. This is due to the department’s continued success garnering external research funding. The fourth floor is abuzz with robust research and training and we are proud of our growing activities. Our expanding research activity in CRB led to our adding an additional administrative assistant to help manage the increasing tasks. Ms. Carmen Schremp joined us in September as Chair’s Assistant. She joins Ms. Colleen Dickey in departmental administrative activities, Ms. Courtney Griese who, after joining last year, has brilliantly mastered our grants administration in CRB, Mr. Teddy Endres, our financial specialist, and Ms. Jen Scheuer, CRB’s Human Resources business partner. Our administrative unit is capably led by Mr. Michael Ferree, who juggles everything from financial planning to personnel issues to near-constant moving and repositioning equipment in the research space. Dr. Brand was the first recruit of the Wisconsin Blood Cancer Research Institute (WBCRI), a new research institute at UW-Madison, founded and directed by our very own Dr. Emery Bresnick, a senior faculty member in CRB whose research career has focused on mechanisms of blood development and disease. In 2021, he successfully launched WBCRI, following his passion to make UW-Madison an international leader in the study and cures for blood cancers. This research institute is growing and thriving under his leadership. Page 4 of this newsletter highlights current goals and activities of WBCRI under his leadership.

Department of Cell and Regenerative Biology

Over the past few years, CRB has redoubled its efforts to lead teaching and training in the stem cell and developmental/regenerative biology space at UW-Madison, adding and revising several graduate level courses in this field. This fall, we received final approval for a PhD minor program in Developmental, Stem Cell and Regenerative Biology. This allows any of our many PhD graduate students (in Cell and Molecular Biology, Genetics, Biomedical Engineering, Integrative Biology, and others) to declare and earn a minor in this burgeoning research area. Beginning in January, we will enroll our first students in the program. One of our new senior faculty, Dr. Nance, has agreed to take on the role of Associate Chair of Teaching and Learning, and he will help ensure our continued growth and leadership in training in this space. This year, we prioritized making room for some of the many success stories of trainees in our department. Please refer to page 6 to read about the many accomplishments of trainees in CRB. On a more somber note, CRB mourned the loss of a former faculty member, Dr. Gary Lyons. For those who knew Gary, he served UW-Madison for many years as an outstanding researcher in cardiac development. Dr. Lyons persevered in his research and teaching career despite serous health battles that would have led most of us to give up. But he continued to battle the odds of his health challenges and dedicated immense energy and passion to teaching medical students, leading the Anatomy and Histology courses in the first-year medical curriculum for many years. After decades of service, he retired from his position of Full Professor in CRB in 2021, and sadly, Dr. Lyons passed away peacefully in his home in Madison in January of 2023. His wife and life partner, Dr. Jayne Squirrel, planned and held a beautiful memorial in his honor in May of 2023. Gary will be missed by many, and many in CRB will continue to hold Gary as a model of academic excellence and service to the institution. In closing, and on behalf of all of us in CRB, we wish you a wonderful 2024 and all good wishes in your endeavors this year. On Wisconsin!


Department News

CRB TO OFFER DEVELOPMENTAL, STEM CELL AND REGENERATIVE BIOLOGY PHD MINOR The 9‐credit doctoral minor in Developmental, Stem Cell and Regenerative Biology provides graduate students with solid course training in the field. In order to coax the human body to regenerate damaged or diseased tissue, a fundamental understanding of developmental and stem cell biology is required. Courses offered through the Department of Cell and Regenerative Biology span a variety of topics in developmental genetics, stem cell biology and organogenesis. Developmental Genetics (CRB 710) is a required course, but students can additionally choose from a range of topics that include gene regulation critical for stem cell maintenance and self-renewal (CRB 640), molecular organogenesis (CRB 650), a specialized course on heart disease and regeneration (CRB 670) and a credited stem cell seminar series (CRB 625). Regenerative Medicine Ethics and Society (CRB 615) is also offered for those students whose academic interests veer more into this arena. Through the many courses offered in this minor program, students will gain foundational knowledge in the field with a focus on critical thinking, oral and written presentation of material. Students interested in advanced academic pursuits in developmental, stem cell and regenerative biology and those interested in pursuing work in stem cell and regenerative medicine for their future careers are encouraged to apply. Required coursework: CRB/GENETICS 710 Developmental Genetics, 3 credits Electives, 6 credits; students can choose up to 6 credits from the courses listed below: CRB/MED HIST 615 Regenerative Medicine Ethics and Society, 3 credits CRB 625 Stem Cell Seminar, 1 credit* CRB 640 Fundamentals of Stem Cell and Regenerative Biology, 3 credits CRB 650 Molecular and Cellular Organogenesis, 3 credits CRB/BME 670 Biology of Heart Disease and Regeneration, 3 credits *Students can take CRB 625 Stem Cell Seminar for up to 3 credits. Minor will be approved and available to enroll in February of 2024. For additional questions or information, please contact: Colleen Dickey at cdickey2@wisc.edu Or Deneen Wellik at wellik@wisc.edu

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WBCRI CONTINUES TO GROW The Wisconsin Blood Cancer Research Institute (WBCRI), instituted in January of 2021 in the UW-Madison School of Medicine and Public Health, is a highly collaborative organization that utilizes multidisciplinary approaches (basic, translational and clinical) to discover blood cancer mechanisms, advance blood cancer diagnosis, prevention and treatment, train research leaders, and serve as an advisory hub for the community. Guiding principles include innovation, collaboration, synergism, collegiality, inclusiveness and diversity. The WBCRI is comprised of 31 faculty members, including 23 laboratory and 8 clinical researchers spanning 11 departments. We are delighted to highlight two recent faculty hires: Dr. Xin Gao, tenure-track Assistant Professor of Pathology, and Dr. Marjorie Brand, Professor of Cell and Regenerative Biology. Dr. Gao conducted brilliant postdoctoral research with Dr. Paul Frenette at Albert Einstein School of Medicine. She discovered that nocioreceptor neurons innervate the bone marrow and are critical determinants of hematopoiesis (Gao et al. Nature 589, 2021), which has important physiological and pathological implications. In addition, Dr. Gao devised innovative strategies for elucidating the functional ramifications of heterocellular interactions in the bone marrow compartment, which led to the identification of a vital functional interaction involving hematopoietic stem cells and macrophages. Dr. Brand is an established senior investigator/Professor who trained at the Fred Hutchinson Cancer Research Center and then joined the University of Ottawa. Dr. Brand has highlevel expertise in diverse realms of hematology and genome science, including T-cell leukemia and innovating multi-omic approaches to discover novel mechanisms underlying hematopoiesis and leukemogenesis. WBCRI is absolutely delighted to welcome Drs. Gao and Brand to our team. Additional WBCRI members that joined in 2023 include: Dr. Rebecca Richards (Pediatrics), Dr. Cathy Lee-Miller (Pediatrics), Dr. Marulasiddappa Suresh (Veterinary Medicine), Dr. Hongtao Liu (Director of Stem Cell Transplantation, Medicine), Dr. Emery Bresnick and Dr. Zhubin Gahvari (Medicine). One of the pressing priorities for WBCRI is to create seamless links between our outstanding UW-Madison School of Medicine and Public Health physicians that treat malignant and non-malignant blood diseases with our professors that lead fundamental and translational research programs. Toward this goal, we have established discussions with physicians that are experts in leukemia and multiple myeloma to explore avenues to develop powerful new molecular diagnostics for early detection of blood cancer and detection of trace levels of cancer cells that re-appear after treatment. In addition, we have initiated a collaboration with the Carbone Comprehensive Cancer Center to develop philanthropic resources to catalyze multiinvestigator research initiatives, as a prelude to enhancing our NIH and foundation funding and transforming blood cancer prevention, diagnosis, and prevention strategies. WBCRI community building continues with a bi-weekly research colloquium, trainee-driven journal club, trainee-faculty chats in which trainees have lunch and engage in informal discourse with a single faculty member, hosting outside invited speakers, and miscellaneous activities, e.g., summer ice cream social. WBCRI faculty are committed to advancing training in multidisciplinary science within the realm of hematology at all levels, and our trainees have recently been awarded American Society of Hematology and International Society of Experimental Hematology Abstract Merit Awards and National Institutes of Health F31 and T32 fellowships. Website: https://wibloodcancer.wisc.edu Twitter: https://twitter.com/wi_blood

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Department of Cell and Regenerative Biology


Faculty Highlights DR. BO LIU JOINS CRB FULL TIME CRB is happy to announce that Dr. Bo Liu officially joined CRB on a full-time basis in April 2023 after being affiliated with the department for many years. Born and raised in China, Bo travelled across the globe to pursue her passion for research and education. Following her PhD training in physiology and biochemistry at State University of New York Downstate Medical Center and postdoctoral research at Columbia University and then Memorial Sloan Kettering, Bo started her independent research career at Weill Cornell Medical School and relocated to UW-Madison in 2008 to lead vascular biology research in Department of Surgery. The mission of the Liu lab is to advance the fundamental knowledge of vascular biology and contribute to healthy living through research and therapeutic development. Toward this mission, Dr. Liu and her trainees are engaged in multiple basic and translational research projects. Their current basic research topics include programmed necrosis, inflammation, cell-cell communications, extracellular vesicles, as well as matrix biology. The translational research of the lab focuses on the pathophysiology, diagnosis, and treatment of aortic aneurysms, arterial stenosis, and venous thrombosis. Bo is a passionate mentor who is committed to training the next generation of cardiovascular investigators. Her mentoring approach emphasizes supporting innovation, independence, and collaboration. Working with the Cardiovascular Research Center and Institute of Clinic and Translational Research, Bo also directs a summer training program for undergraduate students and co-directs the KL2 program for junior faculty.

DR. JEFF DILWORTH LINKS INFLAMMATION TO IMPAIRED MUSCLE REGENERATION Jeff Dilworth and his research team study how muscle stem cells function to regenerate muscle tissue and how the environment they live in can influence their ability to repair muscle damage. The capacity of muscle to regenerate is necessary to replace, grow and repair our skeletal muscle throughout our lives. As we age, maintaining muscle mass becomes increasingly difficult, a result of changes in the effectiveness of our muscle stem cells. Focusing on the role of epigenetics in determining how the hardwired DNA blueprint in our muscle cells is packaged to ensure that the genes necessary for efficient regeneration are turned on, the Dilworth lab is working to understand how to reverse the decline in muscle regenerative capacity as we age. Recent work from their group (Science, 2022) showed that muscle stem cells are impaired in their ability to regenerate in conditions of inflammation. This finding is important as chronic inflammation is a hallmark of aging and suggests that the decreased ability of muscle stem cells to maintain our muscle mass in aging is partially due to the fact that they reside in an environment of inflammation within our bodies. This work also identified hyaluronic acid as a key molecule that protects muscle stem cells from inflammation when we are young, allowing for efficient muscle regeneration despite inflammation caused by muscle injury. Unfortunately, as our bodies age, the muscle stem cells make less of the protein that produces hyaluronic acid. Moving forward, the Dilworth lab is working to understand how to use epigenetic approaches to increase the production of the protein that makes hyaluronic acid so that our muscle stem cells can function properly and effectively throughout our lifetime.

DR. JEREMY NANCE JOINS CRB Jeremy is joining CRB this fall from New York University School of Medicine, where he has been since starting his lab in 2004. Using C. elegans as a model system, his lab is investigating how interactions between cells contribute to organ formation and morphogenesis. Projects in the lab include how cell contact triggers apicobasal polarity, how primordial germ cells are regulated by their surrounding niche, and how small tubes form within cells. The lab’s research uses a combination of cell biological, genetic, and live imaging approaches, and will be a part of the Center for Quantitative Cell Imaging (CQCI) located in the Bock Laboratories building. In addition to his fascination with developmental cell biology, Jeremy has a strong interest in graduate education and mentoring. Outside of the lab, you might find Jeremy with a pair of binoculars hanging from his neck as he learns the local birding spots, or riding bikes with his partner William. He is very excited to be joining CRB and interacting with all of the members of the department.

DR. MARJORIE BRAND USES MULTI-OMICS TO IDENTIFY LEUKEMIA INITIATING CELLS T-Acute Lymphoblastic Leukemia (T-ALL) is a very aggressive blood cancer that is more common in children and younger adults. Even with intensive chemotherapy including allogeneic hematopoietic stem cell transplantation, 40-50% of patients will relapse. At present, there are no efficacious therapies available for relapsed T-ALL and these patients inevitably die from their disease. The laboratory of Marjorie Brand is studying the mechanism of leukemia development in T-ALL. Using a multi-omics approach that gives a global view of changes in RNA and protein expression, the goal of her research is to decipher how the altered function of transcription factors in blood cells leads to leukemia. In particular, her lab is focusing on how transcription factors regulate the formation of Leukemia Stem Cells (also called Leukemia-Initiating Cells), a group of cells that are capable of evading the cytotoxic effects of standard chemotherapy by entering a dormant or quiescent state. These studies are important because patient relapse is the result of reactivation of these quiescent leukemia-initiating cells. While the rarity of these cells within a tumor has traditionally made them extremely difficult to identify and characterize, recent advances in technologies that allow the study of large numbers of individual cells has made it possible to isolate the elusive leukemia-initiating cells. Having recently moved to the University of Wisconsin, the Brand lab is collaborating extensively with a large spectrum of scientists ranging from clinicians to computational biologists to determine how leukemia-initiating cells function in the progression of disease. These studies will ultimately lead to the identification of new therapeutic strategies targeting leukemia-initiating cells to prevent relapse.

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Student Success Stories CAROLINA DE MEDEIROS VIEIRA Carol is a recent graduate of UW-Madison, holding a Bachelor of Science degree in Cell and Molecular Biology. She is currently working as a Research Intern in the Lo Sardo laboratory, where she is gaining valuable skills and experience before taking the next step in her academic journey towards graduate school. In early 2021, as a sophomore undergraduate student, Carol embarked on her research journey in the Lo Sardo lab. Her research is centered on cardiovascular genetic risk factors and their varying impacts on diverse human genetic ancestries. Carol’s work revolves around a fascinating project that delves into the non-coding regions of the genome, particularly those linked to cardiovascular disease risk. She is investigating how these regions, which exhibit significant diversity across different genetic ancestries, affect the cells of the vasculature. Carol was the very first member to join the Lo Sardo lab shortly after its launch at CRB in the Fall of 2020. Despite her young age, she quickly established herself as an essential pillar of the developing laboratory. Her growth as a promising young scientist has been remarkable. Carol’s journey towards a career in science began early, as she sought opportunities for hands-on experiments during her high school years. Her first exposure to the lab environment came in the summer of 2018 at Stanford, when she was still a pre-college student in Brazil. During those few weeks, she had her first encounter with cell culture and cardiovascular research. Upon entering college, Carol initially pursued a bioengineering major, but in her sophomore year, after joining the Lo Sardo lab, she discovered her passion for Cell Biology, prompting her to change her major to Cell and Molecular Biology. Carol’s time in the lab allowed her to become proficient in basic molecular biology techniques and gain experience with a wide array of protocols and experimental settings. She soon progressed to working with human induced pluripotent stem cells, gaining exposure to various human cell cultures. Carol’s expertise extends to the realm of iPSCs, where she adeptly manages differentiation into vascular smooth cells, endothelial cells, neurons, and astrocytes. Her insatiable thirst for knowledge and willingness to embrace new challenges have transformed her into a fine young scientist who consistently performs at a high level, exceeding expectations. It’s no exaggeration when her lab-mates say, “the lab would collapse without Carol.” During her three years at the Lo Sardo lab, Carol has had numerous opportunities to present her independent work. She has confidently delivered oral presentations at the CVRC and showcased her research through poster presentations at multiple UW-Madison events and international conferences. Remarkably, she has delivered six poster presentations in just two years. Carol’s exceptional work and unwavering dedication have not gone unnoticed. She received a CVRC undergraduate summer fellowship in 2022 and an AHA summer undergraduate fellowship in 2023. The AHA fellowship provided her with the opportunity to attend the New York Stem Cell Foundation conference, in October 2023, where she was selected to deliver a poster presentation. In her spare time, Carol channels her energies into the Badger Ballroom team, where she finds joy in dancing and competing on behalf of UW-Madison. Now, with her impressive journey, Carol is gearing up for her next step: applying for graduate school in the upcoming fall. Best of luck, Carol! Your journey so far has been remarkable, and there are undoubtedly many more achievements awaiting you in the future.

METTI GARI With childhood dreams of becoming a scientist, Metti Gari’s dedication to education and research is leading her down a path to success. Metti is a 4th-year international student from Ethiopia who joined the Ponik lab in the fall of 2020. Metti has expressed a strong interest in pharmaceutical drug development and translational cancer research. Her ultimate goal is to return to Ethiopia to improve health care and education, especially for women, within her home country. Metti’s commitment and hard work have already translated into tremendous growth and scientific progress. Guided by her plan, Metti entered graduate school with the self-motivation to achieve her training goals. Starting early in her graduate career she often peppered her advisor with questions about the current therapeutic approaches to breast cancer and specifically about the role of the ECM in breast cancer progression. Her thoughtful and inquisitive nature is also evident through her engagement in her project. Metti can often be found in the lab reading research papers, finishing experiments, or analyzing data. Her current work aims to develop a novel anti-cancer peptide therapy that targets the extracellular matrix. Metti has made significant progress on this challenging and important project. She has determined the distribution and safety of the peptide using pre-clinical models of breast cancer. She has established protocols and expanded her research skills by mastering intravital imaging. This study also leverages her strength in team research as she interfaces with multiple labs to further define the mechanisms and therapeutic efficacy of this peptide. In addition to her research productivity, Metti is also very active with science outreach. She is the Chair of Fundraising and Scholarships for the UW-Madison chapter of Graduate Women in Science (GWIS). In this capacity, she intends to make a substantial impact on the advancement of women in science here at UW-Madison. Scientific achievements to date: • Two co-authored manuscripts (J Controlled Release 2022 and APL Bioengineering 2023) • 2022 ASMB image contest winner • 2023 UW-CCC Minter Graduate Student Research Award • Invited Speaker at the 2023 Tissue, Matrix, and Pathobiology Meeting • Finalist for a PhRMA Predoctoral Fellowship.

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Department of Cell and Regenerative Biology

Metti Gari, PhD candidate in Molecular and Cellular Pharmacology


Department News

IN MEMORIAM: Gary Lyons, PhD. September 02, 1957 - January 30, 2023

Gary Lyons, PhD.

CRB was saddened to learn of the death of longtime CRB professor Dr. Gary Lyons on January 30, 2023. During his tenure at UW, Gary was very passionate about science and teaching. In his lab, he mentored undergraduate and graduate students, post-doctoral fellows, and visiting professors; published over 130 scientific papers and book chapters, and especially enjoyed collaborating with a variety of colleagues. He was an enthusiastic, approachable and admired instructor for first year Medical students and served on a number of UW and community committees, of which he was particularly honored to serve on Medical School Admissions Committees, the Disability Accommodation Advisory Committee and the Embryonic Stem Cell Research Oversight Committee. Gary received a number of academic and teaching awards, but he was most proud of the two Distinguished Teaching Awards conferred upon him by his students. Gary will be missed by all who had the opportunity to know and learn from him.

CRB WELCOMES NEW CHAIR’S ASSISTANT CARMEN SCHREMP CRB was happy to welcome Carmen Schremp to our administrative team in late September! She will be primarily assisting Dr. Wellik as an executive assistant as well as providing general support to the department. Carmen has called Madison home for the majority of her life, and one of her favorite joys is strolling around town with her little dog, Pablo. Prior to joining CRB, she honed her skills as a manager at a local Pilates studio and spent over five years as an administrative assistant/manager at Autohandler, a local luxury automotive business. When she is not engaged in work, she enjoys reading and writing, as she is an aspiring author. An interesting tidbit about Carmen is that she earned her black belt in Martial Arts at the tender age of 10. She is excited to embark on this new adventure as a member of the Cell and Regenerative Biology team!

DR. ANITA BHATTACHARYYA’S RESEARCH HIGHLIGHTED IN WISCONSIN STATE JOURNAL FEATURE The Oct 24th feature entitled “UW effort to map Down syndrome brain raises prospect of treatment for disorder” highlights the work in Dr. Bhattacharyya’s lab in a celebration of 25 years since UW CRB Dr. Jamie Thomson’s seminal contribution to stem cell research, publishing on the isolation and growth of human embryonic stem cells. The article can be accessed here: https://madison.com/news/local/business/health-care/down-syndrome-uw-madisonstem-cells/article_9deebaf2-64a3-11ee-9638-0f5505a5f20d.html

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DONATE TODAY! While the mission and activities of the UW Department of Cell and Regenerative Biology is supported by the great people of the State of Wisconsin and our cutting-edge research, it is only through the generosity of our donors that allows us to fully realize our potential. Please consider making a gift to the department via the UW Foundation at: www.supportuw.org/giveto CRBExcellenceEndowment Or please contact Dr. Deneen Wellik or Michael Ferree to discuss options.

To make a gift by mail, checks may be made out to: The University of Wisconsin Foundation (please include fund #132587161) and sent to: UW Foundation U.S. Bank Lockbox Box 78807 Milwaukee, WI 53278-0807 Questions? Please contact Brad Green; (608)308-5354; brad.green@supportuw.org

CONTACT CRB 1111 Highland Ave. Room 4403 WIMR II Madison, WI 53705

Department Chair Deneen Wellik, PhD. wellik@wisc.edu

Phone: (608) 265 – 3295

Department Administrator Michael Ferree, MBA. CMA. michael.ferree@wisc.edu

Email: info@crb.wisc.edu


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