Tumor Signaling and Angiogenesis Program


Betty S. Pace, MD

Betty S. Pace, MD

Tumor Signaling and Angiogenesis Program
Professor, Pediatrics
Professor, Biochemistry and Molecular Biology
Professor, Graduate Studies
Interim Section Chief, Pediatric Hematology/Oncology
Francis J. Tedesco Distinguished Chair, Pediatric Hematology/Oncology
Director, Pediatric Sickle Cell Program
Member, Vascular Biology Center


 

Georgia Cancer Center
1410 Laney Walker Blvd., CN-4112
Phone: 706-721-3626 office
Phone: 706-721-6895 laboratory
Email: bpace@augusta.edu

*Research Summary*

My laboratory research program involves developing new therapies for people with sickle cell disease. We are developing new drugs and genetic ways to increase the expression of fetal hemoglobin to block the negative effects of sickle hemoglobin. Several new agents are being tested in my laboratory using cells in culture and the sickle cell mouse model.

*Research Interest*

 

Research Program

For over 20 years, research in my laboratory has focused on erythroid development as it relates to hemoglobin synthesis and globin gene regulation with the goal to design novel strategies to induce fetal hemoglobin synthesis for treating sickle cell disease. In the mid-1990s my laboratory pioneered in vivo drug treatment in the µLCRAγ transgenic mouse and later the 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. These agents are currently in clinical testing as novel fetal hemoglobin inducers. More recently the work in my 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 among others differentially expressed in children with low and high fetal hemoglobin levels.

Training Programs

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 also serve as director of the Hemoglobinopathy Translational Skills Development Core (HTRC) program funded by NHLBI. We have supported the training of five junior faculty at Augusta University.  

Pediatric Sickle Cell Program

I am fully engaged as a member of the Augusta University Sickle Cell Research Center. As the Director of the Pediatric Sickle Cell Program we provide medical services for over 800 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 telemedicine program to increase access to care for children in South Georgia to improve standard of care for hydroxyurea therapy and genetic education for sickle cell trait. We conduct clinical trials and genetic studies to enhance translational research conducted in my laboratory.

*Selected Publications*

  1. Peterson KR, Costa FC, Fedosyuk H, Neades RY, Chazelle AM, Zelenchuk L, Fonteles AH, Dalal P, Roy A, Chaguturu R, Li B, Pace BS. A cell-based high-throughput screen for novel chemical inducers of fetal hemoglobin for treatment of hemoglobinopathies. PLoS One 9:e107006, 2014.
  2. 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.
  3. Umapathy NS, Gonzales J, Makala LH, Xu H, Biddinger P, Pace BS.. Impaired pulmonary endothelial barrier function in sickle cell mice. Haematologica pii: haematol.2016.153098.
  4. Liu L, Pertsemlidis A, Ding LH, Story MD, Steinberg MH, Sebastiani P, Hoppe C, Ballas SK, Pace BS. Original Research: A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease. Experimental Biology Medicine (Maywood) 241:706-18, 2016.
  5. Hossain MA, Shen Y, Knudson I, Thakur S, Stees JR, Qiu Y, Pace BS, Peterson KR, Bungert J. Activation of Fetal γ-globin Gene Expression via Direct Protein Delivery of Synthetic Zinc-finger DNA-Binding Domains. Molecular Therapy Nucleic Acids 5:e378. doi: 10.1038/mtna.2016.85, 2016. 
  6. Zhu, X, Li B, Pace BS. NRF2 Mediates γ-Globin Gene Regulation and Fetal Hemoglobin Induction in Human Erythroid Progenitors. Haematologica, pii: haematol.2016.160788, 2017.
  7. Pace BS, Makala LH, Liu L, Sarkar R, Narla M, Takezaki M, Dixon G, WernerE, 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 of Hematology. E pub August 30, 2017

*Awards, Funding, and Patents*

AWARDS

Lifetime Diversity Champion Award, University of Texas at Dallas, 2010

Augusta University, Faculty Senate Basic Science Faculty Award, 2013

Black History Month Faculty Recognition Celebration-“Recognition of the best and brightest African American Faculty”, Augusta University, 2016

SEBM Burt Sobel Preclinical and Translational Best Paper Award for 2017, “A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease” April 2017

Honorific Award for Leadership in Promoting Diversity, American Society of Hematology, December 2017

FUNDING

The Role of Endothelin-1 in Sickle Cell Disease-Translational Research Skills Development Core (TRC), National Heart Lung and Blood Institute, $5,792,500 (2013-2018); U01 HL117684; Pace (Director HTRC; Co-Investigator)

State of Georgia Newborn Screening Program, Georgia Department of Public Health, $311,000 (2015-2020); Pace (Director, Pediatric Sickle Cell Program)

Gamma Globin Induction: Molecular and Cell-Based Strategies, National Heart Lung and Blood Institute $1,000,000 (2014-2018); R01 HL069234 Pace (PI/PD)

PRIDE-Functional and Translational Genomics of Blood Disorders, National Heart Lung and Blood Institute, $1,375,000 (2014-2018); R25 HL085070; Pace (PI/PD)

State of Georgia Newborn Screening Program, Georgia Department of Health, $311,000 (2015-2020); Pace (Director, Pediatric Sickle Cell Program)

Implementation of Medical Homes for Evidence Based Care of Adolescents/Adults with Sickle Cell Disease, National Heart Lung and Blood Institute, $62,000 (2016-2022); 1U01HL134004; Kutler/Gibson (PI), Pace (Co-Investigator)

Preclinical characterization of PB-04 as a fetal hemoglobin inducer in β-YAC transgenic mice, Leidos Biomedical Research, NIH/NCATS, $329,895 (2016-2017); Pace (PI/PD)    

TRAINEE FUNDING

Gamma Globin Induction: Molecular and Cell-Based Strategies, National Heart Lung and Blood Institute, Diversity Supplement $79,037 (2016-2018); R01 HL069234-11S1 Pace (PI/Mentor), Nicole Lopez (graduate student) 

American Society of Hematology Minority Medical Student Award Program, $10,000 (2017-present), Augusta University, Pace (Mentor), David Foreman (medical student)

*Research Team*

Mayuko Takezaki, MS
Mayuko Takezaki, MS

Research Manager
Biaoru Li, MD, PhD 
Biaoru Li, MD, PhD

Senior Research Scientist
Xingguo Zhu, PhD 
Xingguo Zhu, PhD

Research Scientist
Becky B. Stone, PhD 
Becky B Stone, PhD

Assistant Professor
Nicole Lopez, BS
Nicole Lopez, BS

Graduate Research Assistant
Aluya Oseghale, MS
Aluya Oseghale, MS

Graduate Research Assistant
David Foreman, BS 
David Foreman, BS

Medical Student-ASH MMSAP Award

 

*Training Program Team*

Natasha Alford, MBA
Natasha Alford, MBA

*Office Coordinator* *HTRC Program Coordinator*
Mary Johnson, MS 
Mary Johnson, MS

*Grant Program Coordinator* *PRIDE Program Administrator *

 

*Pediatric Sickle Cell Program Team*

Judi Schweitzer
Judi Schweitzer

Office Specialist
Ann Sapp 
Ann Sapp

Office Associate
Cynthia Williams, SR LPN 
Cynthia Williams, SR LPN

Newborn Screening Nurse
Thomas Clements, PA-C, RRT 
Thomas Clements, PA-C, RRT

Physician Assistant
Krystal Stone, BBA 
Krystal Stone, BBA

Research Assistant
Caroline Wilder, BS
Caroline Wilder, BS

Research Assistant
Dominik Barnes, BA
Dominik Barnes, BA

Research Assistant