Alvarez, the Tireless Self-Starter
The Tyvek suit slips over legs and arms and chest, zips up, and Nadine Alvarez, Ph.D., connects the respirator to the tubes, to the helmet, and then seals the protective material closed. She enters the Biosafety Containment Level 3 (BSL-3) unit, pulling the door closed behind her.
Then the work begins.
Alvarez has been a key collaborator and contributor to some of the largest projects at the Hackensack Meridian Center for Discovery and Innovation (CDI) practically since its inception. She is a scientist who has worked with deadly pathogens for a number of years, helping to advance major research projects that have impacted thousands if not millions of people worldwide, but she barely breaks a sweat in her day-to-day job. Right now she is working with pathogens which are growing in prevalence and resistance - the bacteria that causes gonorrhea, and the monkeypox virus. But she continues to be involved in a number of ongoing projects including drug discovery and surveillance of variants of the COVID-19 virus, SARS-CoV-2. She has been able to reinvent herself relentlessly, to go where the science is needed today.
“I prefer to work inside the BSL-3,” said Alvarez recently. “You need to plan very well, and it involves a lot of diligence - but it is a safe place under very controlled biosafety conditions, and you need to be focused. But that’s the work I like.”
“Nadine Alvarez is an extremely valuable contributor to so much of the work that we do,” said David Perlin, Ph.D, chief scientific officer and executive vice president of the CDI. “A big part of the reason we can take on so many research projects is because we have someone like her making the work happen at such a critical juncture.”
Evolving Pathogens, Expertise
Alvarez’s work has evolved with the needs of her scientific institutions, encompassing a wide variety of germs.
Tuberculosis vaccines were her original field of expertise. Growing up in Cuba, she is a product of the University of Havana, where she pursued degrees up to and through her doctorate. It was at the Finlay Institute of Vaccines that she worked through her fellowship and as a research associate. Ultimately, she led the development of both prophylactic and therapeutic vaccine candidates for tuberculosis, by getting into the nitty-gritty part of the work: the preparation of liposomes and proteoliposomes derived from mycobacterial components and assessment of their immunogenicity and protective efficacy in animal models of progressive TB infection, as well as tissue processing, staining, and detailed assessment of infected samples for disease progression and vaccine impact.
The work naturally led to a move to the United States for her postdoctoral fellowship, working with TB’s cousins, the non-tuberculous mycobacteria, or NTM. Her work brought her into the Public Health Research Institute (PHRI) laboratories of Thomas Dick, Ph.D., and Veronique Dartois, Ph.D., who focused on all mycobacteria, NTM as well as TB. NTM, while mostly not as virulent as its more-well-known cousin, is a distinct and emerging health threat all on its own - and Alvarez was glad to be able to tackle it.
“It was a good experience to get, because it involves drug discovery - and that’s what I wanted to do,” recalled Alvarez recently.
Alvarez joined in with many PHRI colleagues when they relocated to the CDI, coming with Perlin,Dick, and Dartois and so many other personnel. Her diligence and reliability expanded her role to managing the mycobacterial research laboratory by 2021.
Covid Twist of Fate
But then, as it did for so many millions, a little virus had big changes in store for Alvarez.
SARS-CoV-2 swept the world in early 2020, and utterly upended many things and well-laid plans. The CDI, which had not been a specialist in viruses before the advent of the pandemic, pivoted to address the needs of New Jersey - and the world. After the initial needs for diagnostics and surveillance, Perlin and colleagues from multiple institutions put together a plan for a federally funded national research consortium which would become known as the Metropolitan Antiviral Drug Accelerator, or MAVDA. The goal was to discover and develop new compounds which would treat not only COVID-19’s virus, but also other coronaviruses that could be future pandemic threats.
Alvarez, who had not specifically worked with viruses before, was up for the challenge. So she switched from the NTM and went down the hall of the CDI’s fifth floor to the Perlin Laboratory, and its exciting new project.
“David is a great PI (principal investigator) because he always provides opportunities,” said Alvarez. “You can go to him with new ideas - and he is always open to listening to what we can do next.”
The work was immediately exciting, she recalled.
“We performed hundreds and hundreds and hundreds of assays, and we started to see the new series of compounds showing promising antiviral potency. It was like, wow. Everyone was excited, because we knew the new modifications we were making were non-toxic, and had improved activity,” she said.
Viruses and Bacteria
Monkeypox is another emerging threat of interest to Alveraz. Starting in 2022 Alvarez became instrumental in leading the hunt for therapeutics for the virus, especially in developing a novel virus inhibitor, while advancing understanding of viral pathogenesis and therapeutic intervention.
The latest priority is a Perlin-led program to develop a novel antibiotic targeting the pathogen causing gonorrhea, part of a federally-funded Center of Excellence in Translational Research (CETR). Like MAVDA, the CETR is a new bacteria-focused national drug accelerator program, powered by a 5-year, $37.8-million NIAID grant.
The CETR group will continue to unite experienced drug developers from academic and pharmaceutical/biotech teams: the CDI, Rutgers University, Merck, and Prokaryotics. Alvarez’s role is to lead one of the five projects within the accelerator: to advance the development of a potent, dual-targeting TriBE-class lead candidate for the treatment of highly drug-resistant Neisseria gonorrhoeae, contributing to the global fight against antimicrobial resistance.
Amid and underpinning all this work, Alvarez specializes in developing and refining ex-vivo assays using human primary cells in an air-liquid interface (ALI) model to simulate the human respiratory environment, enabling more accurate evaluation of infection dynamics and host immune responses.
Travel, Books, and Photography
Alvarez grew up the daughter of an optical-technician mother, and a father who traveled the world for his work. But it was Alvarez’s own natural curiosity and a nose for books which led her down the path of scientific discovery. Throughout her life, one page leads to another, and books and books later, she has found herself into new realms of knowledge.
Her own daughter is in her 20s, living in Florida with aspirations of a career in psychology.
Her love, outside the laboratory, is to travel and take pictures. She and her husband remain great friends who are very much in love - and they cherish sharing the new experiences of new sights worldwide, she said. But there is always time between trips for reading and for cooking, she said. Home is where the heart is.
</h1alvarez,>“I love people to come to my home, and I just cook for them and do small dinners and gatherings,” she said.