Margaret Goodell

Last updated

Margaret A. Goodell
Margaret Goodell 2.jpg
Education
Known forStem Cell Research
Children3
Scientific career
FieldsStem Cells, Cancer Biology
Institutions
Website https://www.goodell-lab.com

Margaret ("Peggy") A. Goodell (born March 23, 1965) is an American scientist working in the field of stem cell research. Dr. Goodell is Chair of the Department of Molecular and Cellular Biology [1] at Baylor College of Medicine, Director of the Stem Cell and Regenerative Medicine (STaR) Center, [2] and a member of the National Academy of Medicine. [3] She is best known for her contributions to understanding how blood stem cells are regulated. [4]

Contents

Goodell has been on the faculty of Baylor College of Medicine since 1997 as a member of the Center for Cell and Gene Therapy, and the Departments of Pediatrics, Molecular and Human Genetic, and Molecular and Cellular Biology. [5] She is the director of the Stem Cells and Regenerative Medicine Center, and is the Chair of the Department of Molecular and Cellular Biology. She holds the Vivian L. Smith Chair in Regenerative Medicine and is the Co-Leader of the Cancer Cell and Gene Therapy program at the Dan L. Duncan Comprehensive Cancer Center. [6] She has received numerous awards for excellence in teaching and research. [7] [8]

Goodell is Chair of the Scientific Advisory Board of the Keystone Symposia, a former President of the International Society for Experimental Hematology, and has served on the board of the International Society for Stem Cell Research. She has also served on several committees, including as the chair of Stem Cells and Regenerative Medicine for the American Society of Hematology. She was an Associate Editor for Blood [9] and serves on the editorial boards of Cell Stem Cell and Cancer Cell .

Education

Goodell began her education at Wesleyan University and moved on to the Imperial College of Science and Technology in London, England, for her final years, where she received her B.Sc. in Biochemistry with Honors in 1986. She went on to earn her Ph.D. at the University of Cambridge in 1991, working at the famous Laboratory of Molecular Biology. She returned to the United States to complete postdoctoral fellowships in Richard Mulligan’s lab at the prestigious Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology and Harvard Medical School. [10]

At MIT, she developed a novel method for isolating blood-forming stem cells from mouse bone marrow based on a fortuitous observation that stem cells efflux fluorescent lipophilic dyes. This "side population (SP)" method became widely used to isolate stem cells from a variety of species and adult tissues, including from cancer stem cells. [11]

Research and career

In 1997, Goodell joined the faculty of Baylor College of Medicine in Houston, Texas, in the Departments of Pediatrics and Molecular and Human Genetics. She is a member of the Center for Cell and Gene Therapy [12] and a founding member and director of the Stem Cell and Regenerative Medicine (STaR) Center. [13] She became Chair of the Department of Molecular and Cellular Biology in 2019.

She served as a board member of the International Society for Experimental Hematology from 2009 to 2012. She was elected president of the Society in 2013 and served until 2014. [14] Additionally, she was a board member of the International Society for Stem Cell Research from 2004 to 2007. [15]

Goodell became well known for her development of a novel strategy to isolate stem cells from tissues of adult animals. She observed that a small “side population” of stem cells rapidly pumped out a fluorescent dye (Hoechst 33342), and that flow cytometry could be used to isolate a relatively pure stem cell population. [16] The paper based on this discovery was published in the Journal of Experimental Medicine in 1996 and has been cited nearly 4000 times. [17] This was a breakthrough discovery that has allowed many other scientists to isolate other types of stem cells, and allowed her lab to isolate hematopoietic stem cells (HSCs) with distinct functional characteristics. This led to two new cornerstones of HSC biology: the concepts of HSC heterogeneity and differentiation bias. [18] The strategy has since been applied to many tissues and organisms, including human cancer stem cells and flatworm stem cells.

Goodell’s strategy for HSC purification allowed her lab to study mechanisms that regulate HSC regeneration, quiescence (when the cell is not going through the cell cycle but retains the ability to differentiate [19] ), differentiation, and aging. The lab discovered new roles in hematopoiesis of several genes, which led to new knowledge of the role of the immune response in controlling HSC responses. This was an important conceptual advance in the field that has created increased understanding of how the immune system can activate HSCs, especially using interferons. In particular, interferon gamma directly regulates HSC activation and that activation is essential for a successful immune response. [20] This development has created a new sub-field of HSC investigation into the relationships between HSCs, immunity, and inflammation. The paper based on these interferon discoveries was published in Nature in 2010 and has been cited over 1000 times. [21]

She has uncovered how the enzyme de novo DNA methyltransferase, DNMT3A — one of the most important tumor suppressors in the blood — contributes to stem cell self-renewal and differentiation in aging, inflammation, and cancer. [22] The ablation of DNMT3A leads to an increase in HSC self-renewal and a decrease in differentiation. [23] DNMT3A mutations contribute heavily to leukemia development and clonal hematopoiesis, and have come to be understood as the most important tumor suppressor in the hematopoietic system.

These interests led her to a suite of novel CRISPR-mediated techniques to investigate the relationship between DNA methylation and gene expression. [24] The Goodell lab investigates the role of DNMT3A in normal and malignant hematopoiesis, and has discovered a new genome feature termed “methylation canyons.” [25]

More than 400 of her peer-reviewed primary research papers have been published in journals including Nature [26] and Blood. [27] She was an associate editor of Blood from 2013 to 2020. [28] Since 2007, she has been a reviewer and served on the editorial board of Cell Stem Cell, and joined the editorial board of Cancer Cell in 2020. In 2024, she published an opinion piece in The Globe and Mail on early cancer detection.

Her current research is focused on the mechanisms that regulate HSCs, and how those regulatory mechanisms go awry in hematologic malignancies. The Goodell Laboratory, which has about 15 students and post-doctoral fellows, studies the effects of stresses, including infection, toxicity, and age, on the behavior of HSCs. The lab also looks at stem cell growth control, as well as the regulation of self-renewal and activation. [29]

Awards and honors

In 2023, Goodell received the Donald Metcalf Award from the ISEH, [30] cementing her legacy as a distinguished figure in the field. She gave the Tobias Lecture at the International Society for Stem Cell Research in 2020. Her remarkable achievements continued with her election in 2019 to the National Academy of Medicine. In 2012, she was awarded the Damashek Prize from the American Society of Hematology, the most prestigious award from the Society nominated by the members themselves to recognize research that has changed the understanding of hematology. [31] In 2011, she was recognized with the Edith and Peter O’Donnell Award in Medicine. From 2006 to 2011, she received the American Heart Association’s Established Investigator Award. In 2006, she was honored with the Stohlman Scholar Award from the Leukemia and Lymphoma Society. In 2004 and 2010, she received the DeBakey Award for Excellence in Research. Alongside these accomplishments, she has received numerous accolades for her teaching and mentorship. Throughout her career, she has mentored more than 50 doctoral students and post-doctoral fellows, many of whom have gone on to successful careers in academia in addition to mentoring a number of residents, clinical fellows, assistant professors, masters' students, undergraduates, and high school students.

Biography

Goodell grew up in Bryan, Ohio with sisters Marian (a founding member and CEO of the Burning Man Project [32] ), Martha (a management consultant), and Melly (a physician). She is the daughter of Joe Goodell, former CEO of American Brass Company, and niece of Grace Goodell, professor of International Development at The Johns Hopkins School of Advanced International Studies. She lives in Houston, Texas with her husband and three daughters.

Related Research Articles

<span class="mw-page-title-main">Haematopoiesis</span> Formation of blood cellular components

Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten billion to a hundred billion new blood cells are produced per day, in order to maintain steady state levels in the peripheral circulation.

<span class="mw-page-title-main">Stem cell</span> Undifferentiated biological cells that can differentiate into specialized cells

In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.

<span class="mw-page-title-main">Bone marrow</span> Semi-solid tissue in the spongy portions of bones

Bone marrow is a semi-solid tissue found within the spongy portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production. It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis. Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow.

<span class="mw-page-title-main">Hematopoietic stem cell</span> Stem cells that give rise to other blood cells

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm.

<span class="mw-page-title-main">CD34</span> Cluster of differentiation protocol that identifies cell surface antigens.

CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.

<span class="mw-page-title-main">Progenitor cell</span> Cell that differentiates into one or a few cell types

A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only differentiate into their "target" cell type. The most important difference between stem cells and progenitor cells is that stem cells can replicate indefinitely, whereas progenitor cells can divide only a limited number of times. Controversy about the exact definition remains and the concept is still evolving.

<span class="mw-page-title-main">Monoblast</span>

Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. Their myeloid cell fate is induced by the concentration of cytokines they are surrounded by during development. These cytokines induce the activation of transcription factors which push completion of the monoblast's myeloid cell fate. Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages. They then are seen as macrophages in the normal peripheral blood and many different tissues of the body. Macrophages can produce a variety of effector molecules that initiate local, systemic inflammatory responses. These monoblast differentiated cells are equipped to fight off foreign invaders using pattern recognition receptors to detect antigen as part of the innate immune response.

<span class="mw-page-title-main">Promyelocyte</span> Granulocyte precursor cell

A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12–20 microns in diameter. The nucleus of a promyelocyte is approximately the same size as a myeloblast but their cytoplasm is much more abundant. They also have less prominent nucleoli than myeloblasts and their chromatin is more coarse and clumped. The cytoplasm is basophilic and contains primary red/purple granules.

The Society for Hematology and Stem Cells is a learned society which deals with hematology, the study of the blood system and its diseases, including those caused by exposure to nuclear radiation. It was founded in 1950, and held its first official meeting in Milwaukee in 1972. Its mission statement is: "To promote the scientific knowledge and clinical application of basic hematology, immunology, stem cell research, cell and gene therapy and related aspects of research through publications, discussions, scientific meetings and the support of young investigators."

<span class="mw-page-title-main">HOXA9</span> Protein-coding gene in humans

Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.

<span class="mw-page-title-main">DNA (cytosine-5)-methyltransferase 3A</span> Protein-coding gene in the species Homo sapiens

DNA (cytosine-5)-methyltransferase 3A (DNMT3A) is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene.

<span class="mw-page-title-main">Sean J. Morrison</span>

Sean J. Morrison is a Canadian-American stem cell biologist and cancer researcher. Morrison is the director of Children's Medical Center Research Institute at UT Southwestern (CRI), a nonprofit research institute established in 2011 as a joint venture between Children’s Health System of Texas and UT Southwestern Medical Center. With Morrison as founding director, CRI was established to perform transformative biomedical research at the interface of stem cell biology, cancer and metabolism to better understand the biological basis of disease. He is a Howard Hughes Medical Institute Investigator, has served as president of the International Society for Stem Cell Research, and is a member of the U.S. National Academy of Medicine, U.S. National Academy of Sciences and European Molecular Biology Organization.

<span class="mw-page-title-main">Haematopoietic system</span>

The haematopoietic system is the system in the body involved in the creation of the cells of blood.

Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). As these cells are short-lived, there needs to be a steady turnover of new blood cells and the maintenance of an HSC pool. This is broadly termed hematopoiesis. This event requires a special environment, termed the hematopoietic stem cell niche, which provides the protection and signals necessary to carry out the differentiation of cells from HSC progenitors. This stem-cell niche relocates from the yolk sac to eventually rest in the bone marrow of mammals. Many pathological states can arise from disturbances in this niche environment, highlighting its importance in maintaining hematopoiesis.

Gordon M. Keller is a Canadian scientist recognized for his research on applying developmental biology findings to in vitro pluripotent stem cell differentiation. He is currently a Senior Scientist at the Ontario Cancer Institute, a Professor at the University of Toronto and the director of the McEwen Centre for Regenerative Medicine.

<span class="mw-page-title-main">Musashi-2</span> Protein-coding gene in the species Homo sapiens

Musashi-2, also known as Musashi RNA binding protein 2, is a protein that in humans is encoded by the MSI2 gene. Like its homologue musashi-1 (MSI1), it is an RNA-binding protein involved in stemness.

Clonal hematopoiesis of indeterminate potential, or CHIP, is a common aging-related phenomenon in which hematopoietic stem cells (HSCs) or other early blood cell progenitors contribute to the formation of a genetically distinct subpopulation of blood cells. As the name suggests, this subpopulation in the blood is characterized by a shared unique mutation in the cells' DNA; it is thought that this subpopulation is "clonally" derived from a single founding cell and is therefore made of genetic "clones" of the founder. The establishment of a clonal population may occur when a stem or progenitor cell acquires one or more somatic mutations that give it a competitive advantage in hematopoiesis over the stem/progenitor cells without these mutations. Alternatively, clonal hematopoiesis may arise without a driving mutation, through mechanisms such as neutral drift in the stem cell population. Clonal hematopoiesis may occur in people who are completely healthy but has also been found in people with hematologic diseases. The clonal population may vary in size depending on the person, where it can be less than 2% of the blood or, at the other end, can sometimes grow close to 100%. The incidence of clonal hematopoiesis has been found to rise dramatically with age. Recent studies have demonstrated that less than 1% of the population under age 40 but approximately 10-20% of the population over age 70 has observable clonal hematopoiesis. Having clonal hematopoiesis has been linked to a more than 10-fold increased risk of developing a blood cancer, though the overall likelihood is still low. Clonal hematopoiesis does not typically give rise to noticeable symptoms, but does lead to increased risk of cardiovascular disease. Patients with solid tumors or lymphoma and clonal hematopoiesis have been shown to have an inferior outcome.

<span class="mw-page-title-main">Christa Muller-Sieburg</span> German-American Immunologist and Hematologist

Christa Edith Muller-Sieburg was a German-American immunologist and hematologist, whose work became central to the understanding of the clonal heterogeneity of hematopoietic stem cells (HSCs). Muller-Sieburg is known for her contributions to the purification of hematopoietic stem cells, the characterization of individual stem cell clones and her revision of the process of hematopoiesis.

<span class="mw-page-title-main">Cynthia E. Dunbar</span> American hematologist

Cynthia Dunbar is an American scientist and hematologist at the National Heart Lung and Blood Institute (NHLBI), which is part of the National Institutes of Health (NIH). She is the Branch Chief of the Translational Stem Cell Biology Branch.

Louise E. Purton is an Australian biologist who is Professor of Medicine and head of the Stem Cell Regulation Laboratory at St. Vincent's Institute of Medical Research in Melbourne. Her research considers the stem cells responsible for the production of blood cells and the regulations of haematopoietic diseases. She was awarded the International Society for Experimental Hematology McCulloch & Till Award in 2022. She has experienced profound bilateral hearing loss since the age of three and has been recognised for her work supporting Equity and Diversity, particularly amongst women and people with disability, and is a member of the AAMRI Gender, Equity and Diversity and Inclusion group GEDI.

References

  1. ↑ "Dr. Peggy Goodell named chair of cell biology". Baylor College of Medicine. August 27, 2019.
  2. ↑ "STaR Center". Baylor College of Medicine. Retrieved October 26, 2023.
  3. ↑ "National Academy of Medicine Elects 100 New Members". October 21, 2019.
  4. ↑ "ASH honors Margaret A. Goodell, Ph.D., with 2012 William Dameshek Prize". EurekAlert!.
  5. ↑ "Molecular and Human Genetics". Baylor College of Medicine.
  6. ↑ "Margaret A. Goodell, Ph.D. | BCM". www.bcm.edu. Retrieved August 30, 2024.
  7. ↑ "2011 O'Donnell Awards Recipients - TAMEST (The Academy of Medicine, Engineering and Science of Texas)". TAMEST The Academy of Medicine, Engineering and Science of Texas.
  8. ↑ Lako, Majlinda; Daher, Susan (June 2009). "Balancing Work and Life: A Conversation with Margaret 'Peggy' Goodell". Stem Cells. 27 (6): 1227–1228. doi: 10.1002/stem.105 . PMID   19489078.
  9. ↑ "Editorial Board and Staff – Associate Editors". Blood. Archived from the original on June 18, 2014.
  10. ↑ "Hematopoietic Stem Cell Biology - Goodell Lab - Baylor College of Medicine, Houston, Texas". www.bcm.edu. Archived from the original on July 15, 2014. Retrieved January 14, 2022.
  11. ↑ Goodell, M. A.; Brose, K.; Paradis, G.; Conner, A. S.; Mulligan, R. C. (April 1, 1996). "Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo". The Journal of Experimental Medicine. 183 (4): 1797–1806. doi:10.1084/jem.183.4.1797. ISSN   0022-1007. PMC   2192511 . PMID   8666936.
  12. ↑ "Margaret A. Goodell, Ph.D. - Center for Cell and Gene Therapy - Baylo…". Archived from the original on June 18, 2014.
  13. ↑ "STaR Center". Baylor College of Medicine. Retrieved October 26, 2023.
  14. ↑ "ISEH Board of Directors". International Society for Experimental Hematology. August 30, 2024. Retrieved August 30, 2024.
  15. ↑ "About". International Society for Stem Cell Research. Retrieved August 30, 2024.
  16. ↑ Goodell, M. A.; Brose, K.; Paradis, G.; Conner, A. S.; Mulligan, R. C. (April 1, 1996). "Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo". The Journal of Experimental Medicine. 183 (4): 1797–1806. doi:10.1084/jem.183.4.1797. ISSN   0022-1007. PMC   2192511 . PMID   8666936.
  17. ↑ "Google Scholar". scholar.google.com. Retrieved August 30, 2024.
  18. ↑ Challen, Grant A.; Boles, Nathan C.; Chambers, Stuart M.; Goodell, Margaret A. (March 5, 2010). "Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1". Cell Stem Cell. 6 (3): 265–278. doi:10.1016/j.stem.2010.02.002. ISSN   1875-9777. PMC   2837284 . PMID   20207229.
  19. ↑ Urbán, Noelia; Cheung, Tom H. (February 8, 2021). "Stem cell quiescence: the challenging path to activation". Development. 148 (3): dev165084. doi:10.1242/dev.165084. ISSN   0950-1991. PMC   7888710 . PMID   33558315.
  20. ↑ Baldridge, Megan T.; King, Katherine Y.; Boles, Nathan C.; Weksberg, David C.; Goodell, Margaret A. (June 2010). "Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection". Nature. 465 (7299): 793–797. doi:10.1038/nature09135. ISSN   1476-4687. PMC   2935898 .
  21. ↑ "Google Scholar". scholar.google.com. Retrieved August 30, 2024.
  22. ↑ Goodell, Margaret A.; Li, Wei; Godley, Lucy A.; Issa, Jean-Pierre J.; Meissner, Alexander; Darlington, Gretchen J.; Lu, Yue; Liang, Shoudan; Gu, Hongcang; Vasanthakumar, Aparna; Bock, Christoph; Berg, Jonathan S.; Jelinek, Jaroslav; Luo, Min; Jeong, Mira; Sun, Deqiang; Challen, Grant A. (January 2012). "Dnmt3a is essential for hematopoietic stem cell differentiation". Nature Genetics. 44 (1): 23–31. doi:10.1038/ng.1009. PMC   3637952 . PMID   22138693.
  23. ↑ Challen, Grant A.; Sun, Deqiang; Jeong, Mira; Luo, Min; Jelinek, Jaroslav; Berg, Jonathan S.; Bock, Christoph; Vasanthakumar, Aparna; Gu, Hongcang; Xi, Yuanxin; Liang, Shoudan; Lu, Yue; Darlington, Gretchen J.; Meissner, Alexander; Issa, Jean-Pierre J. (December 4, 2011). "Dnmt3a is essential for hematopoietic stem cell differentiation". Nature Genetics. 44 (1): 23–31. doi:10.1038/ng.1009. ISSN   1546-1718. PMC   3637952 . PMID   22138693.
  24. ↑ Gundry, Michael C.; Brunetti, Lorenzo; Lin, Angelique; Mayle, Allison E.; Kitano, Ayumi; Wagner, Dimitrios; Hsu, Joanne I.; Hoegenauer, Kevin A.; Rooney, Cliona M.; Goodell, Margaret A.; Nakada, Daisuke (October 2016). "Highly Efficient Genome Editing of Murine and Human Hematopoietic Progenitor Cells by CRISPR/Cas9". Cell Reports. 17 (5): 1453–1461. doi:10.1016/j.celrep.2016.09.092. PMC   5087995 . PMID   27783956.
  25. ↑ Huang, Yung-Hsin; Chen, Chun-Wei; Sundaramurthy, Venkatasubramaniam; Słabicki, Mikołaj; Hao, Dapeng; Watson, Caroline J.; Tovy, Ayala; Reyes, Jaime M.; Dakhova, Olga; Crovetti, Brielle R.; Galonska, Christina; Lee, Minjung; Brunetti, Lorenzo; Zhou, Yubin; Tatton-Brown, Katrina (January 2022). "Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor". Cancer Discovery. 12 (1): 220–235. doi:10.1158/2159-8290.CD-21-0560. ISSN   2159-8290. PMC   8758508 . PMID   34429321.
  26. ↑ Johnson, R. Paul; Mulligan, Richard C.; Sieff, Colin A.; Grupp, Stephen A.; DeMaria, MaryAnn; Marks, Douglas F.; Kim, Hyung; Rosenzweig, Michael; Goodell, Margaret A. (December 1997). "Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species". Nature Medicine. 3 (12): 1337–1345. doi:10.1038/nm1297-1337. PMID   9396603. S2CID   22879109.
  27. ↑ Search Results for author Goodell MA on PubMed .
  28. ↑ "Editorial Board and Staff". Blood. August 30, 2024. Retrieved August 30, 2024.
  29. ↑ "PPM1D Mutations Drive Clonal Hematopoiesis in Response to Cytotoxic Chemotherapy" – via www.youtube.com.
  30. ↑ "Awards - International Society for Experimental Hematology". www.iseh.org. Retrieved October 26, 2023.
  31. ↑ "Honorific Award Nominations". www.hematology.org. Retrieved August 30, 2024.
  32. ↑ "Marian Goodell". Burning Man Journal. June 21, 2019.
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