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General blog about anything and everything of everyday's life.

20. May 2019

‘Life as Research Scientist’: Angel Byrd, Cell Biologist

For years, Brown University M.D./Ph.D. student Angel Byrd had dedicated herself to studying how immune system cells capture invading fungal pathogens. Like those cells, called neutrophils, she had seized on seemingly every opportunity that had come her way.

In high school she was the valedictorian and won a 10-year Gates Millennium Scholarship. As an undergrad at Tougaloo College she earned the opportunity to do summer research in China on gene expression and was named a Leadership Alliance scholar. Later at Brown she earned a research internship at drug giant Eli Lilly, and has piled up awards for research posters. Twice she met with senators and representatives on Capitol Hill on behalf of the American Society for Biochemistry and Molecular Biology. And after she won a coveted United Negro College Fund/Merck Graduate Fellowship in 2011, she sparkled on televisions around the country in a segment featuring her on BET.

Recently we spoke with Miss Byrd to know more about her research work, why this is important, and how life as a research scientist is. But before proceeding with our questions to Miss Byrd, let us learn on her childhood from her own words:

Angel Byrd: ‘Although life is filled with challenges and obstacles, my motto in life is I can do ALL things through Christ who strengthens me. I am striving for a 100 because a 99 and 1/2 just won’t do!’

Angel Byrd: ‘Although life is filled with challenges and obstacles, my motto in life is I can do ALL things through Christ who strengthens me. I am striving for a 100 because a 99 and 1/2 just won’t do!’

I was born in Jackson, MS.  My childhood (until about age 5 after my father’s death) was spent in a small town known as Edwards, MS, which is approximately 30 miles west of Jackson…

My mom has always been very hard working and also my father from what I can remember …

Although, we did not have much money, my mom, especially, has always sacrificed (working 2 jobs, etc.) a lot to make sure that my brothers and I had the things that we needed.  She actually still does this even today.  She is one of the many reasons why I strive so hard with hopes that one day I can take care of her…

Thank God, my mother (my pride-and-joy) is still living. Her name is Willie Jean Byrd…

My father passed away due to a tragic car accident (Willie H. Byrd)…

My stepfather’s name is Myron Smith (although he and my mother are no longer together for a number of absurd reasons, she has taught and raised us to respect him regardless of the problems that the two of them had)…

good times/ bad times in life

Good times – enjoying life in a small rural town (Edwards) where everyone knows EVERYONE and we were all like family; great history and culture; reflecting on days where I would sit on the porch with my grandmother (maternal-Ada T. Wallace), walk to the local corner store with my 2 older brothers (Genada and Jonathan Byrd) and cousins (Marcus Wallace, Letitia Wallace, and others), playing out in the yard; attending church service and revival (sometimes under a tent outside) with my grandmother; everyone was willing to help one another out; performing very well in grade school; being crowned Miss Callaway High School; graduating Valedictorian and being inducted into the Hall of Fame…

Bad times – my father’s death; having to leave private school (majority white) due to financial difficulties and because my mom felt that I was losing my identity as an African American;  dealing with how my brothers rebelled and trying to make sure that I stayed focused and strived to do my very best in the midst of it all…

So, here we go with our questions to Miss Byrd:

Q. Let us start with your research topic. What is your research area? Will you please tell us a bit more on this? What did you find?

Angel Byrd: The armament of neutrophil-mediated host defense against pathogens includes the extrusion of a lattice of DNA and microbicidal enzymes known as Neutrophil Extracellular Traps (NETs). The receptor:ligand interactions and intracellular signaling mechanisms responsible for elaborating NETs were determined for the response to Candida albicans. Since the host response of extravasated neutrophils to mycotic infections within tissues necessitates contact with extracellular matrix (ECM), this study also identified a novel and significant regulatory role for the ubiquitous matrix component fibronectin (Fn) in NET release. We report that recognition of purified fungal pathogen-associated molecular pattern β-glucan by human neutrophils causes rapid (≤ 30 mins) homotypic aggregation and NET release by a mechanism that requires Fn. 

Q. Why is this important? (i.e. why should the general public care about this?)

Angel Byrd: We report a new regulatory mechanism of neutrophil clustering/aggregation and NETosis in which the extracellular matrix (components that stabilize the physical structure of tissues) is a key component of the rapid anti-fungal response.

Q.  Is this truly new information or does it confirm what other researchers have found?

Angel Byrd: Other researchers have reported NETosis in response to various pathogens, including C. albicans.  However, our work is unique in that it identifies neutrophil aggregation, the receptor:ligand mediation of NET formation and the independence of the neutrophil respiratory burst in this rapid response.

Q. What are the possible clinical implications of your findings?

Angel Byrd: To further understand and optimize the host defense against fungal infections, such as C. albicans.  This is important for every human being, but especially people who suffer from a compromised immune system, for example, those who have HIV.  There are also a variety of illnesses that are caused by defective or deficient neutrophils, which also increases the risk for fungal infections among many others.  Understanding the behavior of neutrophils, such as how they migrate into clusters/aggregates and form NETs could be very helpful in improving health outcomes. 

It is also important to mention that there are clinical scenarios where the cells can cluster too much in addition to producing too many NETs, which can cause complications. Therefore, deciphering the intricacies of this process will aid in the balance and better health outcomes.

From the drug development perspective, many antifungal are available.  However, pathogens have developed a way to resist certain treatments and the therapy is no longer affective. Therefore, understanding neutrophilic responses, such as cell clustering/aggregation and NET formation can lead to drugs that target these mechanisms and can heighten or decrease the response as necessary.

Angel Byrd: ‘My experience at Lilly has demonstrated to me the power and resources of industry and has sparked an interest in bridging academic medicine and industry collaborations’.

Angel Byrd: ‘My experience at Lilly has demonstrated to me the power and resources of industry and has sparked an interest in bridging academic medicine and industry collaborations’.

Q. What do you want the general public to understand about your findings?

Angel Byrd: Neutrophils are the most numerous white blood cell, which are important cells in host defense mechanisms. Among various other mechanisms, these particular cells protect us by forming clusters/aggregates and NETs.  Having a compromised immune response, a low number (neutropenia) or defective neutrophils is the primary risk factor for Candidiasis, a frequent infection that is associated with 40-80% mortality and causes about 10,000 deaths per year in the United States.  Modifying the neutrophil response in these various clinical situations can be very beneficial to suffering patients.

Q. How did you land here. Was it your goal?

Angel Byrd: How does one approach an elusive multifactorial disease that is taking its toll not only in the U.S. but all over the world, has tripled in the last three decades, is a risk factor for cardiovascular disease, morbidity, stroke, kidney failure, and has been reported as the seventh leading cause of death? Twenty-four million adults and children are affected with diabetes in the US, in addition to fifty-seven million who are affected with pre-diabetes. If these statistics continue, by year 2020 it is estimated that more than half of Americans will have diabetes. An unfortunate paradox and disparity is that a higher incidence of diabetes is seen in the African American population, yet we have less access to adequate healthcare to manage this disease. We know that there are genetic risk factors, such as Y-box protein regulation of the protein tyrosine phosphatase, PTP-1B, which may explain insulin resistance observed in type 2 diabetes. Likewise, behavioral factors such as diet, and social factors such as location all play a role in the onset of diabetes. For example, in Mississippi where I grew up, the numbers are staggering. As of 2009, it is the state with the highest number of cases of childhood and adult obesity, and has the 2nd highest ratio in the nation of those suffering from diabetes. It is these questions and other complex medical issues that brought me to where I am now, an MD/Ph.D. student in the Pathobiology program at Brown University. I acknowledge four key experiences thus far as a prelude to the life I aspire to. That is a life that combines basic research, clinical medicine, drug discovery, research in health disparities, and educating and inspiring the next generation of scientists and physicians.

I chose to attend Tougaloo College, a historically black college and university (HBCU) that is known for its academic excellence, its traditions for training outstanding future physicians and scientists, and its relationship with Brown University. One of my professors, Dr. Jinghe Mao, witnessed my academic performance and offered me a position to conduct research that focused on sequencing the Regina ranavirus (RRV) genome. This instance marked the beginning of my research training. I was fascinated by being able to ask scientific questions and undergo a detailed exploration to determine answers. In addition to this and other wet lab experiences I had the opportunity to conduct clinical research as well. As an undergraduate, I participated in the Jackson Heart Study (JHS), which focuses on cardiovascular diseases and health disparities in the African American population in Jackson, Mississippi. I also conducted research at Miriam Hospital’s Weight Control and Diabetes Research Center. This study was intriguing to me as I observed the complex relationship between obesity and type 2 diabetes. This was one of the experiences that sparked my interest in pursuing diabetology. Given the richness of my undergraduate experience in both basic and clinical research projects, I was keen to combine both and made the decision to pursue an MD/Ph.D. at Brown University.

After completing my Ph.D., I will transition back into medical school to finish the remaining two clinical years, finally attaining my MD/Ph.D. My ultimate goal is to become a Pediatric Endocrinologist, primarily focusing on childhood obesity which results in the onset of type 2 diabetes. I plan to also be active in basic research aimed at understanding the pathophysiology of diabetes with a focus at the protein level. My experience at Lilly has demonstrated to me the power and resources of industry and has sparked an interest in bridging academic medicine and industry collaborations. I hope to contribute to the development of drugs that are tolerated in children. This is an ongoing goal within pharmaceutical companies, but one that is rather challenging.  Notably, I am also committed to continuing research that focuses on inequalities that exist among African Americans.

Q. How many hours a day you spend for study. How you arrange other side of your life like social activities so to say?

Angel Byrd: The hours that I spend a day studying varies.  My growth in Christ and school are my main priorities daily.  Therefore, my daily goals revolve around these very important factors.  I start early AM, usually with coffee and reading my Bible to stage the day.  Then, I adventure into the experiment that I will be doing.  In the midst of the experiment, I read literature, think about my next experiments, analyze data from previous experiments, discuss results with my PI and labmates, etc. during incubation times.  This daily process can take anywhere from 12 hours to 12 hours+.  I commit myself to lab and my experiments and accomplish all else once this task is completed. For example, a pleasant surprise that my scientific/medical training has afforded me is that I have been able to use it as a platform for addressing social issues that are important to me. In particular, increasing scientific literacy among our citizens, closing the racial gap in education as well as access to quality healthcare are ideals I am committed to. I am especially invested in helping Mississippians. Mississippi, as well as the nation as a whole, struggles with the scientific literacy of citizens and the widening racial gap in education. I look forward to using my platform as a scientist to address these important social disparities, which have huge implications in medicine and society. In this regard, I had the opportunity and honor to impact Congress when I was asked to represent Brown University to lobby for National Institutes of Health (NIH) funding on Capitol Hill. During this effort, I spoke to Rhode Island senators and representatives in conjunction with the American Society for Biochemistry and Molecular Biology (ASBMB). At a time when all federal spending is being scrutinized I was pleased to be able to make a stand for increasing the budget for the NIH, and thus research and education.

My current path has also allowed me not only to have many wonderful mentors and advisors, but to be a mentor myself. One of the most satisfying aspects of my training to date is that I frequently have the opportunity to speak to high school and college students about a career in science and medicine. I know first-hand the path that can be taken without proper guidance. One of the most challenging aspects of my personal journey was witnessing the rebellion of my brothers after my father passed away. This reached a climax when I learned my brother dropped out of high school and had been convicted of murder despite the care and nurture of my mother. If my mentorship can encourage someone to stay focused and prevail then I have succeeded in this mission.

In addition, I attend church service weekly, lead community service initiatives, play the violin with my PI, visit my family in Mississippi , and spend time with friends as time permits.

Q. Are you satisfied with your results? What about your publications?

Angel Byrd: I am very satisfied with my results!  In my opinion, understanding the PMN response to fungal infections and the role that NETs are playing is truly intriguing and renders very gratifying results, which advance the field of study.  On the other hand, I am not satisfied with my number of publications.  For the work that I put in, I wish I had more to show for it, contributing more to science.  I will continue to work my hardest as I wrap up my PhD and hopefully I will have the opportunity to publish more manuscripts.

Q. If you would not be at your current profession, what other options would you consider for your career?

Angel Byrd: I have been in pursuit of my MD/PhD for many years and I cannot envision myself doing anything else.  However, when I was in high school, I often declared that I wanted to be a doctor and/or a lawyer.

In addition to our questions, here are excerpts from ‘Responses for BET representative – UNCF Evening of Stars 2011’

–  Although life is filled with challenges and obstacles (during the 1st 2 years of medical school I was diagnosed with a learning disability, I battled with successfully passing the USMLE-Step1, had to change labs and my thesis project  after 2 years, etc.)…My motto in life is I can do ALL things through Christ who strengthens me:  with my eyes I can visualize all of the goals that I will achieve, with my mind I can conquer all of life’s many obstacles, with my hands I can mold my life into an authentic masterpiece, with my soul I can continue to hope, dream and long for the day when my life unfolds into a joyous miracle…I am striving for a 100 because a 991/2 just won’t do!

–  My daddy named me so it is something that I take very seriously.  It is my daily mission to live up to my name and be the Angel that I know he wants me to be.  I know he is smiling on me daily.  Although, he is not here physically I am confident that he is witnessing all of my accomplishments, blessings and achievements and he is saying “That’s my Angel” as he did when I was born…

–  I always tell people that I have 2 sets of wings (because of my name – Angel Byrd) and the limit is beyond the sky on all that I hope and will accomplish throughout my life!

–  I always remember all that I have been blessed with and I make it my priority to make sure that I am also helping someone else out along the way (community service, other students, my younger cousins, etc.).  Although I know that there is only so much that I can do at this point in my life, I do believe that every little bit counts and one day I will be able to give back in many more ways.  Paying it forward will always remain high on my priority list….

Thank You.  

*Download a pdf version of the interview

*** For interested readers, here is a list of publications of Miss Angel Byrd:

PUBLICATIONS:

Byrd, AS, O’Brien, XM, Johnson, CM, Lavigne, LM and Reichner, JS. An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to C. albicans. Journal of Immunology. 2013, 190(8):4136-4148.

Byrd, AS, Yu, K, Johnson, CM, O’Brien, XM, Lavigne, LM, Salomon, AS and Reichner, JS: Recognition of fungal β-glucan by human neutrophil CR3 9CD11b/CD18) results in homotypic cell aggregation and rapid formation of extracellular traps by a mechanism that depends on α5β1. 1st Joint Meeting of Pathology and Laboratory Diagnostics, 2012 September 12-15, Udine, Italy. Am J Pathol 2012, 181(Suppl):S1 Abstract AMT1.

Johnson, CM, Byrd, AS and Reichner, JS: Signaling molecules involved in homotypic aggregation of human neutrophils in response to fungal β-glucan. 1st Joint Meeting in Pathology and Laboratory Diagnostics, 2012 September 12-15, Udine, Italy. Am J Pathol 2012, 181 (Suppl):S1 Abstract AMT1.

Byrd, AS, Yu, Kebing, Johnson, CM, Lavigne, LM, Salomon, AR and Reichner, JS (2012). Recognition of fungal β-glucan by human neutrophil CR3 results in homotypic aggregation and Neutrophil Extracellular Traps. FASEB J. 26, 276.3.

Johnson, CM, Byrd, AS and Reichner, JS (2012). Mechanistic role for α3β1/CD151 and the neutrophilic fungal response to β-glucan. FASEB J. 26, 276.4.

Byrd, AS, Yu, K, Salomon, AR and Reichner, JS (2011). Characterization of β-glucan treated human neutrophils provides a phospho-site-specific global proteomic analysis of downstream phosphorylation events. FASEB J. 25, 793.6.

Byrd, AS, Yu, K, Morin, NA, Johnson, CM, Salomon, AS and Reichner, JS (2011). Phosphoproteomic analysis of differentially ligated human neutrophils elucidates downstream tyrosine phosphoproteomic events. FASEB J. 25, 38.9.

Willett, H, Byrd, AS, Johnson, CM and Reichner, JS. β2 integrin Complement Receptor 3 (CR3) regulation of Signal Transduction Activator f Transcription 3 (STAT 3) in neutrophil function. Annual Biomedical Research Conference for Minority Students (ABRCMS). 2011 (abstract).

Johnson, CM, Byrd, AS, Loosley, AJ and Reichner, JS (2011). Signaling molecules differentiate single versus dual ligation of Complement Receptor 3. FASEB J. 25, lb325.

Byrd, AS, Morin, NA, Lavigne, LM and Reichner, JS (2009). β2 integrin Complement Center 3 (CR3, CD11b/CD18) regulation of neutrophil function. FASEEB J. 23, 568.2.

*Note: Other sources to the interview

–  Brown University research news

–  Responses for BET representative – UNCF Evening of Stars 2011’

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