Patient-Oriented Research Mentoring for the Investigation of Acute and Chronic Sickle Cell Disease Pain

The overall goal of this K24 application, “Patient-Oriented Research Mentoring for the Investigation of Acute and Chronic Sickle Cell Disease Pain” is for a mid-career physician-scientist, Dr. Amanda Brandow, to enhance her mentoring skills and develop the next generation of clinical investigators who can advance acute and chronic pain research in individuals with sickle cell disease (SCD). Severe, acute and chronic debilitating pain are the most common complications of SCD, an inherited hemoglobinopathy affecting ~100,000 people in the US and 1 in 365 Black individuals. Despite the same β-globin mutation resulting in hemoglobin S that leads to severe SCD, there is inter-individual variability in the frequency and severity of pain. Improved understanding of why this inter-individual variability exists is essential to the development of individualized pain treatment. Using plasma-based gene transcription we have shown individuals with SCD have a unique inflammatory signature compared to controls that is associated with increased pain frequency and worse pain-related patient-reported outcomes. We have also shown there is significant inter-individual variability in this inflammatory signature. There is a critical knowledge gap in the reasons, other than chronic red blood cell sickling, that contribute to the variation in inflammatory expression and pain phenotypes in individuals with SCD despite the same underlying SCD-related biology. With this K24, Dr. Brandow will expand her current research program to investigate this variability and has proposed new research, conducted as a mentored project, that seeks to investigate the impact of social determinants of health (SDOH) on SCD pain outcomes as mediated by the immune system. Individuals with SCD have multiple SDOH stressors such as poverty, food insecurity, and housing instability that are shown to be positively associated with increased health care utilization for pain and worse patient-reported outcomes. However, the biology that connects SDOH stressors to worse SCD health outcomes in not understood and will be explored in this K24 project. Dr. Brandow has a track record of research and mentoring but she requires additional time to cultivate the careers of individuals interested in SCD patient-oriented research. Therefore, Dr. Brandow’s K24 award goals are to enhance her mentoring skills and build the careers of trainees and junior faculty who are interested in a SCD patient-oriented research career. This K24 award will afford Dr. Brandow with protected time for mentoring and expansion of her research program that will serve as a platform for mentees to also build their careers. Through support from this K24, Dr. Brandow will strengthen her skillset in two focused areas: 1) Mentorship to develop careers of trainees and 2) Immunologic basis of pain. The research environment at the Medical College of Wisconsin and her “Mentoring the Mentor” Scientific Advisory Committee will facilitate her goals. Ultimately, this award will increase our understanding of SCD pain and develop the future generation of clinical investigators to enhance SCD knowledge for years to come for this underserved population