Education
Begley studied medicine at the University of Melbourne starting in 1972 and finishing in 1978. During this time, he completed his M.B., Ph.D.in cellular and molecular biology, and B.S. [8]
C. Glenn Begley is a hematologist and oncologist who is the CEO of BioCurate, an Australia-based joint venture between the University of Melbourne and Monash University that was launched in 2016. [1] Previously, he worked at the California-based biotech company Akriveia Therapeutics as their chief scientific officer. His other previous positions include global head of hematology and oncology research at Amgen, senior vice president and chief scientific officer at TetraLogic Pharmaceuticals, and executive director of the Western Australian Institute of Medical Research.
He studied medicine at the University of Melbourne. [1] He is known for a study he co-authored in 2012 in which he found that only 6 out of 53 (11%) of landmark preclinical studies of cancer drugs could be reproduced. [2] [3] [4] [5] He was elected to the American Society for Clinical Investigation in 2000. [6] Begley was elected Fellow of the Australian Academy of Health and Medical Sciences in 2015. [7]
Begley studied medicine at the University of Melbourne starting in 1972 and finishing in 1978. During this time, he completed his M.B., Ph.D.in cellular and molecular biology, and B.S. [8]
In the 1980s Begley did an apprenticeship under Donald Metcalf who was a pioneer of hematology in Australia. [9] This was at the Walter and Eliza Hall Institute of Medical Research, the oldest medical research institute in Australia. [10] This was for 3 years while Begley was a PhD student. [11] Begley worked at Amgen in California from 2002-2012. Amgen is a biotechnology company that scientific research into drug development strategies and then markets them. [12] He was the vice president and global head of hematology/oncology research.
On 15 March 2012 C. Glenn Begley was announced as the senior vice president of research and development at TetraLogic Pharmaceuticals in Pennsylvania. He worked there from 2012-2016. [13] During this time, he also worked as a Non-Executive director and senior clinical advisor at Oxford BioTherapeutics (2012-2017). [14] [15] Begley is currently the CEO of BioCurate. The aim of BioCurate is to recognize potential in biomedical research and then invest to accelerate the process of converting the research into medicine and therapies. [16]
In the 1980s, Begley’s research was mainly done with Don Metcalf. They were featured on several papers together. From the scientific articles released at that time that he was the Chief Author of, the research areas included colony-stimulating factors (CSF) and their relevance to white blood cells and the immune response in vitro. [17] [18] In 1985 Begley, Metcalf and N.A. Nicola published a paper centring on granulocyte colony-stimulating factor’s (GCSF) effect on differentiation of white blood cells. This paper found that GCSF was affected differently to other colony stimulating factors and the paper was cited 136 times. [19] Begley published a paper in 1986 that has 182 cites involving injecting mice with Multipotential CSF (M-CSF) then comparing white blood cell count in control mice. The results showed that M-CSF increased the monocyte and neutrophil count by more than 200% and the eosinophil count by 1000%. This paper showed the importance of CSF in hematopoietic repopulation in living organisms. It was cited 225 times. [20]
In the 1990s his articles were focused around genes and proteins. The main gene looked at was the SCL gene and how it links to cancer. Begley continued his work from the 80’s into colony-stimulating factors (specifically GCSF) and in 1992 was published in the Lancet. This paper had important work outlining how CSF increases platelet recovery after chemotherapy. [21] He also researches the developing nervous system and the different roles that proteins, white blood cells and genes play. In 1999 he released an article which he was the co-author of that was solely on SCL and the relationship with T cells and T lymphocytes. This paper concluded with an “Unresolved Issues” [22] section which provides unanswered questions about SCL leading to more potential research in the future for Begley. [23] [24]
In the 2000s his work on Thrombopoietin and a protein coded by this gene was released. This is a hormone that regulates platelet production. He also had his most cited paper in 2007 titled "Genome-wide association study identifies novel breast cancer susceptibility loci" [25] with 2518 cites. Begley was also involved in more work with mice that found that bone marrow cells are not a contributor to endothelium of tumors. In 2006 Begley contributed to work on EpoR on another highly cited paper (262) in the field of hematology. [26]
In the 2010s more reflective scientific articles were released by Begley that comment on how his career and experience has shaped his view today. They talk about how scientific integrity is essential for research, the challenges involved with oncology research and how to avoid making mistakes when researching and producing drugs. This aligns with his time at BioCurate and TetraLogical Pharmaceuticals where his work involved drug related ventures and investing in therapies. [27] [28]
In 2015 Begley published a tribute to Don Metcalf. Begley and Metcalf worked together for 15 years. Begley claims Metcalf was a "teacher, role model, mentor, colleague and friend" to him and that he had a resounding impact on his life. In this article Begley explains how Metcalf shaped his view of scientific integrity and how science should have a passing of knowledge from experienced scientists to newer ones. [29]
Thrombopoietin (THPO) also known as megakaryocyte growth and development factor (MGDF) is a protein that in humans is encoded by the THPO gene.
Granulocyte colony-stimulating factor, also known as colony-stimulating factor 3, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
Donald Metcalf AC FRS FAA was an Australian medical researcher who spent most of his career at the Walter and Eliza Hall Institute of Medical Research in Melbourne. In 1954 he received the Carden Fellowship from the Anti-Cancer Council of Victoria; while he officially retired in 1996, he continued working and held his fellowship until his death in December 2014.
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.
Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein contains 152 amino acids and its molecular weight is 17 kDa. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors. It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.
The myeloblast is a unipotent stem cell which differentiates into the effectors of the granulocyte series. It is found in the bone marrow. Stimulation of myeloblasts by G-CSF and other cytokines triggers maturation, differentiation, proliferation and cell survival.
Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It causes a temporary condition with a low absolute neutrophil count and because the neutrophils make up the majority of circulating white blood cells it places the body at severe risk of inflammation and infection. In comparison to severe congenital neutropenia, it responds well to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count, shortens the cycle length, as well decreases the severity and frequency of infections.
Interleukin 5 (IL5) is an interleukin produced by type-2 T helper cells and mast cells.
Sargramostim is a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) that functions as an immunostimulator.
The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the placenta.
Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell.
The granulocyte colony-stimulating factor receptor (G-CSF-R) also known as CD114 is a protein that in humans is encoded by the CSF3R gene. G-CSF-R is a cell-surface receptor for the granulocyte colony-stimulating factor (G-CSF). The G-CSF receptors belongs to a family of cytokine receptors known as the hematopoietin receptor family. The granulocyte colony-stimulating factor receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates cell proliferation and differentiation into mature neutrophilic granulocytes and macrophages.
The granulocyte-macrophage colony-stimulating factor receptor also known as CD116, is a receptor for granulocyte-macrophage colony-stimulating factor, which stimulates the production of white blood cells. In contrast to M-CSF and G-CSF which are lineage specific, GM-CSF and its receptor play a role in earlier stages of development. The receptor is primarily located on neutrophils, eosinophils and monocytes/macrophages, it is also on CD34+ progenitor cells (myeloblasts) and precursors for erythroid and megakaryocytic lineages, but only in the beginning of their development.
T-cell acute lymphocytic leukemia protein 1 is a protein that in humans is encoded by the TAL1 gene.
GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of blood-forming, lympathic system-forming, and other tissue-forming stem cells. GATA2 is encoded by the GATA2 gene, a gene which often suffers germline and somatic mutations which lead to a wide range of familial and sporadic diseases, respectively. The gene and its product are targets for the treatment of these diseases.
CFU-GEMM is a colony forming unit that generates myeloid cells. CFU-GEMM cells are the oligopotential progenitor cells for myeloid cells; they are thus also called common myeloid progenitor cells or myeloid stem cells. "GEMM" stands for granulocyte, erythrocyte, monocyte, megakaryocyte.
Talimogene laherparepvec is a biopharmaceutical drug to treat melanoma that cannot be operated on; it is injected directly into a subset of lesions which generates a systemic immune response against the patient's cancer. The final four year analysis from the pivotal phase 3 study upon which TVEC was approved by the FDA showed a 31.5% response rate with a 16.9% CR rate. There was also a substantial and statistically significant survival benefit in patients with earlier metastatic disease and in patients who hadn't received prior systemic treatment for melanoma. The earlier stage group had a reduction in the risk of death of approximately 50% with one in four patients appearing to have met, or be close to be reaching, the medical definition of cure. Real world use of talimogene laherparepvec have shown response rates of up to 88.5% with CR rates of up to 61.5%.
Roland Mertelsmann is a German hematologist and oncologist. He was a professor at the Freiburg University Medical Center, Department of Internal Medicine I (Oncology/Hematology). Mertelsmann is known for his scientific works in the fields of hematology, oncology, gene therapy and stem cell transplantation.
Microtransplantation(MST) is an advanced technology to treat malignant hematological diseases and tumors by infusing patients with granulocyte colony-stimulating factor (G-CSF) mobilized human leukocyte antigen (HLA)-mismatched allogeneic peripheral blood stem cells following a reduced-intensity chemotherapy or targeted therapy. The term "microtransplantation" comes from its mechanism of reaching donor cell microchimerism. Chemotherapy is used by lower doses only to destroy cancer and partially suppress patient’s immune system, which will be reinitiated by donor’s stem cells soon after transplantation, and will play a role as recipient-versus-tumor (RVT) effect combining donor cells’ graft-versus-tumor (GVT) effect. Donor’s stem cells, which have been processed, will also accelerate functional recovery of recipient’s hematopoietic stem cells, greatly reducing infections and transplant-related mortality. Practices of microtransplantation has shown none graft-versus-host disease (GVHD) till present, thus immunosuppressive drugs for relieving GVHD wouldn't be necessary. Possible mechanisms of the successful avoidance of GVHD include donor cell microchimerism, less-toxic cells processed prior to transplantation, and the preservation of host immune system that is capable of resisting the GVH alloresponse. Moreover, as HLA-mismatched stem cells are employed, donor availability is extremely extended.
Lenzilumab is a humanized monoclonal antibody that targets colony stimulating factor 2 (CSF2)/granulocyte-macrophage colony stimulating factor (GM-CSF).