Betty S. Pace, MD
Professor of Pediatrics
Francis J. Tedesco Distinguished Chair Pediatric Hematology/Oncology
Professor of Biochemistry and Molecular Biology
Professor of Graduate Studies
Director, Comprehensive Sickle Cell Program Telehealth Center
Over the last three decades, the research focus in the Pace laboratory has been erythroid development as it relates to globin gene regulation and hemoglobin synthesis. As an NIH-funded physician-scientist, in the mid-1990s my laboratory pioneered in vivo drug treatment in the µLCRAγ transgenic mouse and later the human β-YAC mouse model. We were the first to demonstrate the ability to induce γ-globin expression using butyrate and 5-azacytidine in β-YAC mice; this model was later used to discover novel short-chain fatty acid derivatives that induce γ-globin. The 5-azacytidie analog, Decitabine is currently in clinical testing as a novel fetal hemoglobin inducer. A second drug Benserazide which is an L-Dopa inhibitor was shown to induce fetal hemoglobin and a phase 1 clinical trial is underway in thalassemia patients. More recently the work in the Pace laboratory was expanded to include microRNA (miRNA) work. We demonstrated a role of miR-34a in γ-globin regulation through silencing the repressor molecule, Stat3. We conducted a genome-wide miRNA screen using reticulocytes isolated from children with sickle cell disease and identified miR-144 and miR29 among others differentially expressed in children with low and high fetal hemoglobin levels. Both miRNA were subsequently shown to induce fetal hemoglobin in sickle erythroid progenitors.
In parallel with my research program, over the last 25 years I have personally trained over 80 individuals including master’s thesis and pre-doctoral candidates, postdoctoral fellows, and junior faculty members to conduct basic and translational research. In 2006, I was awarded a National Heart Lung and Blood Institute (NHLBI) R25 grant to establish a Summer Institute Programs to Increase Diversity (SIPID), with subsequent renewals as the PRIDE-Functional and Translational Genomics of Blood Disorders Program. I serve as program director. The primary focus of PRIDE is technical skills enhancement, intense mentoring, and teaching grant writing skills to aide mentees in achieving extramural funding. We have trained 76 underrepresented junior faculty members under my leadership.
I am fully engaged as a member of the Augusta University Sickle Cell Research Center where we provide medical services for over 600 children at the Children’s Hospital of Georgia in Augusta and five outreach clinics in rural South Georgia in partnership with the Georgia Department of Public Health. More recently we established a Sickle Cell TeleHealth Program to increase access to care for children in South Georgia and improve standard of care for hydroxyurea therapy and genetic education; I currently serve as Director. Also, we participate in clinical trials with pharmaceutical companies and conduct genetic studies to increase therapeutic options for individuals with sickle cell disease.
Boosalis MS, Sangerman JI, White GL, Wolf RF, Shen L, Dai Y, White E, Makala LH*, Li B, Pace BS, Nouraie SM, Faller DV, Perrine SP. Novel Inducers of Fetal Globin identified through High Throughput Screening (HTS) are active in vivo in anemic baboons and transgenic mice, PLoS One, 2015; 10(12):e0144660
Krishnamoorthy S, Pace BS, Gupta D, Sturtevant S, Li B, Makala L, Brittain J, Moore N, Vieira B, Thullen T, Stone I, Li H, Hobbs WE, Light DR. Dimethyl Fumarate Increases Fetal Hemoglobin and Provides Vascular Protection and Heme Detoxification in Sickle Cell Disease Transgenic Mice. Journal Clinical Investigation, Insights, 19;2, pii: 96409, 2017. doi: 10.1172/jci.insight.96409.
Zhu X, Xi C, Thomas B, Pace BS. Loss of NRF2 function exacerbates the pathophysiology of sickle cell disease in a transgenic mouse model. Blood pii: blood-2017-10-810531
Pace BS, Makala LH, Liu L, Sarkar R, Narla M, Takezaki M, Dixon G, Werner E, Maihle N, Jeffe DB, Rice T, González J. Enhancing diversity in the hematology research workforce: A mentorship program to improve the odds of success for early career investigators. American Journal Hematology. 92:1275-1279, 2017. doi: 10.1002/ajh.24899.
Li B, Zhu X, Hossain M, Guy C, Xu X, Bungert J, Pace BS. Fetal hemoglobin induction in sickle erythroid progenitors using a synthetic zinc finger DNA-binding domain. Haematologica 103(9):e384-e387, 2018.
Starlard-Davenport A, Smith A, Vu L, Li B, Pace BS. MiR-29b mediates epigenetic mechanisms of γ-globin gene activation. British Journal Haematology, 186(1):91-100, 2019. doi:10.1111/bjh.15870
Li B, Ward CM, Zhu X, Starlard-Davenport A, Takezaki M, Berry A, Ward A, Wilder C, Neunert C, Kutlar A, Pace BS. MIR-144 Mediated NRF2 Gene Silencing Inhibits Fetal Hemoglobin Expression in Sickle Cell Disease. Experimental Hematology. 70:85-96.e5, 2019.
Oseghale AR, Zhu X, Li B, Peterson KR, Nudelman A, Rephaeli A, Xu H, Pace BS. Conjugate prodrug AN-233 induces fetal hemoglobin expression in sickle erythroid progenitors and β-YAC transgenic mice. Blood Cells Molecules and Disease. 2019 Jul 9;79:102345. doi:10.1016/j.bcmd.2019.102345.
Liu L, Zhu X, Yu A, Ward CM, Pace BS. δ-Aminolevulinate induces fetal hemoglobin expression by enhancing cellular heme biosynthesis. Experimental Biology and Medicine (Maywood). 2019 31:1535370219872995. doi:10.1177/1535370219872995.
Zhu X, Xi C, Ward A, Takezaki M, Shi H, Peterson KR, Pace BS. NRF2 mediates γ-globin gene regulation through epigenetic modifications in a β-YAC transgenic mouse model. Experimental Biology and Medicine (Maywood). 2020 245:1308-1318. doi: 10.1177/1535370220945305.
Biaoru Li, PhD
Chithra Palani, PhD
Mayuko Takezaki, MS
Natasha Alford, MBA