Project Summary/Abstract This application is to request a renewal of the BLR&D Research Career Scientist (RCS) award for Dr. Catarina Hioe. Dr. Hioe is a Research Health Specialist (GS14 Step 6) at the James J. Peters VA Medical Center (JJP VAMC), Bronx, NY, and a tenured Professor of Medicine at the Icahn School of Medicine at Mount Sinai. She joined the VA in 1998 when she initiated her research laboratory with funding from the Merit Review Entry Program at the VA New York Harbor Healthcare System–Manhattan. In 2015, she moved her lab to the JJP VAMC. She received her first RCS award (10/1/12-9/30/17), plus a one-year Cost Extension through 9/30/18 in part for recovery from Superstorm Sandy (10/29/12). She successfully renewed the RCS award for the period of 4/1/2019-3/31/2024. Despite the lab closure during the first wave of COVID-19 in New York City (March-September 2020) and pandemic-related disruptions through the rest of 2020 until 2022, Dr. Hioe’s lab continues to excel, as evidenced by an array of accomplishments in each of the key measures that are highlighted in this application. Since 1998, Dr. Hioe has built a VA research program to study HIV immunology and pathogenesis. This program is also supported by a robust non-VA research program. The Hioe lab is investigating the immunogenic and pathogenic properties of the HIV envelope (Env), a heavily glycosylated protein that interacts with the host to influence virus transmissibility and infectivity. In particular, Dr. Hioe’s studies have focused on antibodies against the HIV Env which mediate not only conventional virus neutralizing activity but also Fc-mediated effector functions and novel factors influencing the antiviral potency of these antibodies. After the emergence of SARS-COV-2 and its rapid spread to cause the COVID-19 pandemic, Dr. Hioe promptly applied her expertise and resources cultivated in the field of HIV to tackle the new coronavirus. Similar to HIV Env, the SARS-CoV-2 Spike glycoprotein is the target for antibodies that neutralize the virus and mediate Fc-dependent activities for clearance of virus particles and virus-infected cells. The Spike glycoprotein is the viral component of all COVID-19 vaccines currently used clinically in the US and other countries, and these vaccines are designed mainly to elicit antibodies. Hence, during the current RCS period, Dr. Hioe’s lab continues to focus on antibody research while expanding the scope to encompass both HIV and SARS-CoV-2. As outlined in her CV (Appendix 1), in the past 10 years Dr. Hioe has published 25 peer-reviewed research papers, 2 review papers and 1 book chapter. She served as first or senior authors for 20 of these articles. Ten publications were published during the current RCS award period to report research findings in the areas of HIV and SARS-CoV-2. She has mentored >35 research trainees throughout her career at the VA; during this RCS award, the trainees include 10 postdoc/junior faculty, 4 graduate, 3 ...