Marcella Sarzotti-Kelsoe, PhD is a Duke Professor in Integrative Immunobiology, an Associate Professor in Surgery, a faculty member of the Duke Human Vaccine Institute, and the Director of the Quality Assurance for Duke Vaccine Immunogenicity Programs.
Briefly describe your upbringing, where you are from, where you went to school
I grew up in Torino (the city in Italy where FIAT cars are made and the winter Olympics were held in 2006), graduated from the University of Torino (Immunology and Microbiology) under Prof. G. Forni, S. Landolfo and F. Dianzani, on the role of Interferon-gamma in response to experimental cancer. My research interest in interferon brought me to Texas (UTMB) as a post-doctoral fellow with Drs. S. Baron and G. Klimpel. Texas became my new home when I married my husband, proudly wore my Lucchese cowboy boots, and drove a red pickup truck. After working as a young faculty member in Baltimore (VAMC and UMAB) I joined the Duke Dept of Immunology (now IIB) in 1998.
What inspired you to pursue a career in science and academia?
From the very beginning of my academic studies I found immunology very intricate and exciting, with so many intriguing and unanswered questions that I decided to join the field. My father inspired me to come to the US to pursue academic research. My husband was always a great supporter of my scientific interests, and we were fortunate to be able to move together twice in Institutions that supported our two independent careers. At Duke I found a stimulating group of scientists that were open to collaborative research.
Describe your research interests and the focus of your work?
My work in basic immunology at Duke Immunology focused on studies of immune system development in early age and following transplantation. My laboratory investigated the early development and function of T cells and their TCR repertoire in neonatal mice and host development of the TCR repertoire in naïve, immunodeficient infants following transplantation. We studied Severe Combined Immunodeficiency Disease (SCID) patients, given bone marrow transplantation (BMT) (with Dr. Buckley, Dept. of Pediatrics, Allergy, Immunology, DUMC), and in DiGeorge syndrome patients given thymus transplantation (with Dr. Markert, Dept. of Pediatrics, Allergy, Immunology, DUMC).
I also studied the TCR repertoire in immunodeficient, HIV-infected individuals. It is during this time that I was given the opportunity by the Duke CFAR Director at the time, Dr. Weinhold, to develop an NIH-required quality program to oversee laboratories testing HIV vaccine human clinical trial specimens for immunogenicity. This was the fork on the road of my scientific career! Since objective guidelines for defining quality in research laboratories analyzing human clinical trial specimens did not then exist, I played a leading role in the creation of a Global Quality Program, later called Quality Assurance for Duke Vaccine Immunogenicity Programs (QADVIP). My colleagues and I designed and implemented rigorous standards for laboratory operation, including operator training, instrument use, assay performance, analysis, validation, document control and archiving. These standards were harmonized and became the Internationally recognized Good Clinical Laboratory Practice (GCLP) Guidelines.
How do you see your research contributing to the department and the broader scientific community?
When conducting basic science, my research on T cell development in early life and following transplantation inspired and was pursued by several Immunology graduate students in my laboratory. It also triggered collaborations and trainings with multiple clinical investigators.
On the quality program side of research I contributed to the broader scientific community as QADVIP oversight grew from 3 to multiple national and international research laboratories (Germany, India, China, Thailand, Brazil, Uganda, S. Africa, UK, Belgium) which we trained on GCLP principles and applications for standardized immunological assays. The Duke School of Medicine (SOM) also appointed me short term as Associate Dean for Advancing Research Practices (Scientific Director), leading efforts to promote quality and data integrity within the Duke (SOM) research community.
Can you discuss any recent publications or projects you're particularly proud of?
- These reports demonstrated that the susceptibility of newborn mice to a virus was an example of immune deviation driven by the relatively high dose of virus encountered by the neonatal immune system. Our report and those of Ridge et al. and Forsthuber et al. in the same issue of Science (22 Mar 1996) used approaches (dose of antigen, type of APCs, adjuvants) known to the immunological community for a long time. However, in combination these approaches offered a simple and comprehensive explanation of immunological non-responsiveness in newborn mice. Sarzotti, M., et al. Science (271): 1726, 1996; Sarzotti, M. Immunological tolerance. Science (letters) (272): 1408, 1996. 28; Fadel S.A., et al. J. Immunol. 169: 3293, 2002.
- These reports described the T cell repertoire development in immunodeficient human infants following transplantation. Sarzotti M., et al. J. Immunol. 170: 2711, 2003; Markert M.L., et al. Blood. 102 (3): 1121, 2003. Sarzotti-Kelsoe M, et al. Blood. 2009 Aug 13;114(7):1445-53;
- This publication details the “harmonization” efforts between International GCLPs, which was led by QADVIP. Sarzotti-Kelsoe M, et al. PLoS Medicine 2009, 6(5): e1000067.
- Here we describe the establishment of an international proficiency testing program for the Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells. Todd C, et al. J Immunol Methods. 2011, Sep 22, 2012; 375 (1):57.
- This publication details technology transfer of the Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells to an international network of laboratories operating under GCLP compliance. Ozaki D.A.,et al. PLoS One. 2012, 7(1):e30963.
- This publication lists the various steps of establishing an international quality assurance program to oversee the integrity of PBMCs’ collection and long-term storage. Sarzotti-Kelsoe M, et al. J Immunol Methods. 2014 Jul; 409:21-30.
- Here we detail the steps taken to implement GCLP in domestic laboratories previously operating in a research and development environment. Todd CA, et al. J Immunol Methods. 2014 Jul; 409: 91-8.
- These papers focus on the validation efforts, with QADVIP quality oversight, for several immunogenicity endpoint assays: Sarzotti-Kelsoe M, et al.. J Immunol Methods. 2014 Jul; 409:147-60; Sarzotti-Kelsoe M, et al. J Immunol Methods. 2014 Jul; 409:131-46; Dennison SM, et al. J Immunol. 2018 Aug 15; 201(4):1315-1326; Schultz A, et al. PLoS One. 2018 Jan 4;13(1):e0190669; Brown EP, et al. J Immunol Methods. 2018 Apr; 455: 24-33; Seaman MS, et al. J Immunol Methods. 2020 Jan, 112736; Epub 2020 Jan 7; Bharadwaj P, et al. J Immunol Methods. 2020 Feb 15:112764. Sawant S, et al. Front. Immunol. 14:1155880. doi: 10.3389/fimmu.2023.1155880; Huang Y, et al. Nature 2021 Dec 14;11(1):23921. doi: 10.1038/s41598-021-03154-6.
How do you balance your work and home life?
This is a question that many applicants graduate students asked me over the years. Raising two daughters and pursuing a career in academia can be done: it requires drive, organizational skills in a household in which the parents are both academic faculty members supporting each other. For fun, outside of work I loved skiing, dancing and traveling with my family (my Gates funding also allowed me to work and visit laboratories in many countries around the world). More recently, I enjoy spending time with family and friends on an island in NC.
How do you stay updated with developments in your field?
The usual way that everyone does: reading, participating in conferences and webinars, talking to peers.
How do you foster an inclusive and supportive environment for your lab members or students?
By listening to the opinions of my team members, offering support and encouragement for their professional growth, training them in honesty, respect, and integrity.
Any other information (personal or work-related) that you’d like to share?
I learned over the years that it is important to keep an open mind for career opportunities that may make you take a turn from your basic trajectory.
I also learned that science goes in 10-15 year waves, as research topics that fell out of favor are bound to make a return to the bench: neonatal immunity is one of them!