Dr. Jay Mandula Explores the Importance of Diversity in Cancer Research

During a summer research internship at Harvard Medical School/Massachusetts General Hospital in 2013, Jay Mandula initially studied neuroscience, focusing on the pathogenic role of aberrantly phosphorylated tau protein in the development of neurodegenerative disease. Although neurodegenerative research was an excellent opportunity to learn fundamental research techniques, Mandula’s final project in the last year of his undergraduate degree awakened a true passion for immuno-oncology. His enthusiasm for immuno-oncology was further fueled by subsequent work at Tampa Bay Research Institute (TBRI), where he pioneered new immunostimulants and led community outreach initiatives focused on cancer immunology and vaccines.

Mandula completed his PhD in cancer immunology and immunotherapy at the University of South Florida, based at Moffitt Cancer Center, adopting bioinformatics-oriented methods to improve the integration of wet and dry lab data for enhanced understanding of immunotherapy. Amidst the COVID-19 pandemic, he also engaged in community outreach about vaccination. Now a postdoctoral researcher at Ohio State University, he continues to explore immuno-oncology, with aspirations of pioneering myeloid-targeted therapies and mentoring the next generation of scientists in a research laboratory of his own in the future.

Laura Lansdowne (LL): Could you elaborate on your current research interests within immuno-oncology? What do you enjoy most about working in STEMM?

Jay Mandula (JM): Throughout my doctoral training and into my postdoctoral research, my primary focus has been on developing a nuanced understanding of cancer-associated myeloid cells. This includes interrogating how the tumor microenvironment drives immunosuppressive myeloid programming and identifying strategies to intercept tumor-derived cues to restore immunostimulatory polarization of myeloid cells and myeloid-dependent antitumor immunity.

Despite the substantial success of anticancer immunotherapy, immunosuppressive myeloid cells remain a major limiting factor constraining durable, curative responses. Furthermore, beyond simply limiting the efficacy of current immunotherapies, therapeutic approaches capable of leveraging the immunostimulatory potential of tumor-associated myeloid cells remain underdeveloped.

Therein, my current and future immunotherapy research objectives are to:

Establish a comprehensive understanding of myeloid intrinsic and tumor-derived extrinsic cues that regulate immunosuppressive versus immunostimulatory myeloid function.
Delineate the mechanistic drivers linking intrinsic or extrinsic signals to impaired induction of antitumor immunity.
Define and develop therapeutic strategies to target central factors that direct immunosuppressive polarization of myeloid cells in cancer.
Interrogate the role of emergency myelopoiesis as a source of tumor-associated immunosuppressive myeloid cells and identify therapeutically targetable drivers of dysregulated myelopoiesis.

I love STEMM for its creativity, intellectual freedom, tangible progress and potential for mentorship intrinsic to this career path.

Some of my proudest achievements have been watching students I have mentored become independent, confident researchers in their own right.

LL: Have you encountered specific challenges in your career related to your identity as an LGBTQIA+ individual? How have you addressed these challenges?

JM: I completed my doctoral research in Florida at the University of South Florida/Moffitt Cancer Center from 2018 to 2023; over this period the Florida government passed several iterations of anti-LGBTQIA+ legislation.

In 2021, Florida passed the “Protections of Medical Conscience Act” which endowed medical providers with the right to discriminate against and decline care to LGBTQIA+ patients if patient care violated their religious conscience.

In 2022, Florida passed the “Don’t Say Gay” Bill (HB 1557) which limited/restricted the freedom of educators to discuss or inform students about LGBTQIA+ topics.

Additionally, in May of 2023, Florida passed Florida Senate Bill 254 which prohibited gender-affirming medical care for minors while also placing significant restrictions on the transition-oriented medical care of adults.

While some organizations ‒ including multiple universities and research centers ‒ chose to speak out against this anti-LGBTQIA+ legislation and show support for their students and faculty, the University of South Florida/Moffitt Cancer Center failed in its support for LGBTQIA+ students and elected multiple times over to say nothing in support of LGBTQIA+ students/faculty/researchers.

It is worth noting that some faculty at USF/Moffitt strongly opposed the institution’s unwillingness to speak out on behalf of its LGBTQIA+ members including my mentor and PI at the time, Dr. Paulo Rodriguez, and other prominent LGBTQIA+ faculty including Dr. Eric Lau, who went above and beyond to support LGBTQIA+ students independently.

As a transgender man receiving lifesaving hormone treatment, this legislation prohibited my ability to receive the medication I need to remain medically stable.

The unwillingness of my doctoral alma mater to support LGBTQIA+ students/researchers and the reality of the loss of essential medical care substantially impacted me during this period of my doctoral research.

Due in no small part to this discrimination, I no longer suggest LGBTQIA+ or other minorities (most notably international students) pursue their PhD or higher education in Florida.

This discrimination also motivated me to come out publicly about my gender identity to serve as a visible and vocal example of how these policies impact the LGBTQIA+ community.

LL: How can institutions better support diversity and inclusion?

JM: As exemplified by the chilling silence of my alma mater, refusing to speak out about overtly discriminatory legislation is one of the most counterproductive approaches institutions can take. Visibly and vocally communicating to students and faculty that they will be supported and protected is essential. In instances where access to medical treatment or similar rights are being infringed upon, institutional provisioning of alternative services or care options can be lifesaving.

LL: In what ways do you think increased visibility of LGBTQIA+ scientists can impact the field of immuno-oncology and STEMM more broadly?

JM: I think increased visibility for LGBTQIA+ researchers can show aspiring LGBTQIA+ scientists in younger generations that their identity does not and should not prohibit their ability to love science and become part of the STEMM community. Acceptance and inclusion are often won via visibility and, in particular, the visibility of more established LGBTQIA+ researchers helps to shift the onus off of the shoulders of early-stage researchers who may be in more vulnerable positions where being out is not safe ‒ especially in areas like Florida.

We need a diversity of perspectives in science, especially cancer research, if we want to make progress in finding treatments and cures. Diverse identities in STEMM should be celebrated not condemned; however, this is not often the case.

In the context of immuno-oncology, LGBTQIA+ patients often receive a lower level of care in cancer diagnosis and treatment, in part due to medical fear surrounding their LGBTQIA+ identity. Additionally, legislation such as that enacted in Florida means that medical providers can outright refuse to treat LGBTQIA+ patients. If patients can see LGBTQIA+ researchers and doctors, they will feel safer seeking care and treatment. Similarly, minority stress, such as overt LGBTQIA+ discrimination, often coincides with increased cancer-associated risk behaviors such as tobacco and alcohol consumption, which place LGBTQIA+ individuals at even higher risk of multiple cancer types.

LL: If you could give one piece of advice to young LGBTQIA+ researchers starting their career, what would it be?

JM: First and foremost, my advice would be: “You belong here, and don’t let anyone tell you that you don’t.” I want young LGBTQIA+ researchers to know that they are not alone and that they have substantial value in contributing to the field of research. I would strongly suggest that younger LGBTQIA+ researchers seek out established LGBTQIA+ mentors in their research field of interest, as they play an essential role in offering advice on how to navigate any professional and interpersonal hurdles that may arise.

Dr. Jay Mandula was speaking to Laura Elizabeth Lansdowne, Managing Editor for Technology Networks.

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