Young Scientists at #LINO23: Kin Israel Notarte – Diving into Virology and Infectious Disease

Kin Israel Notarte, participant of #LINO23, is a first-year PhD Pathobiology student at the Johns Hopkins University School of Medicine. With more than forty publications, his primary research interests lie in the fields of virology, vaccinology, immunology, and infectious diseases. Due to his research in the field of HPV, he would have liked to exchange ideas with Nobel Laureate Harald zur Hausen in Lindau.

My journey as a scientist commenced during my high school years. I was part of a research project investigating the potential anticancer properties of Philippine macroalgae and this experience sparked my deep interest in scientific inquiry. This endeavour garnered recognition, leading to our second-place win in the Intel Philippine Science Fair and selection as a finalist for the 2009 Intel International Science and Engineering Fair (ISEF) held in Reno, Nevada. Motivated by my newfound passion, I embarked on my academic journey by pursuing a Bachelor’s degree in Biology at Silliman University. During this phase, I had the privilege to be mentored by Professor Gary Wessel from Brown University in Rhodes Island. My thesis focused on developmental biology, with a specific emphasis on investigating the tubulin destabilising potential of chemicals from macroalgae using sea urchin embryos as an animal model. My relentless pursuit for higher learning led me to completing a Master of Science in Microbiology from the University of Santo Tomas (UST) under the mentorship of Professor Thomas Edison dela Cruz. During this time, I delved into studying the pharmacologic properties of chemicals sourced from marine-derived fungi against cancer, pathogenic bacteria, and Trypanosoma congolense – the causative agent of animal trypanosomiasis.

As my educational journey progressed, my exposure to the healthcare setting while earning my medical degree further nurtured my enthusiasm for research that directly impacts patient care. This inspired me to pursue a PhD after earning Doctor of Medicine (MD) from UST, with the intent of bridging the gap between basic research and clinical practice to directly benefit patients.

The Impact of Viruses on Human Health

The field of virology is captivating due to the profound implications of viruses on human health. Notably, viruses have left enduring imprints in the human genome as remnants of ancestral infections, and their role in triggering widespread infectious disease outbreaks such as HIV/AIDS and COVID-19 is striking. Projections indicating that infectious diseases will surpass all other causes of death globally by 2050 highlight the urgent need for extensive virology research. To delve deeper into this field, I have chosen to focus my PhD dissertation at Johns Hopkins on HIV diversity and its impact on transmission, disease progression, and treatment outcomes. Under the tutelage of Professor Susan Eshlemann, I aim to contribute to the understanding of HIV dynamics, ultimately aiding in the development of more effective prevention and treatment strategies.

The future of virology research holds tremendous promise as it encompasses unraveling the origins, transmission, and evolution of emerging viruses, while simultaneously advancing the development of effective treatments and cutting-edge diagnostic tools. The importance of research in virology was demonstrated by the SARS-CoV-2 pandemic.

Strategy Shift Due to COVID-19

When the Philippines recorded its first community transmission of COVID-19 in March 2020, it marked a turning point for me as a second-year medical student. The subsequent surge in cases led to a nationwide lockdown, and my medical education shifted to online learning, disrupting the traditional face-to-face classes.

As someone passionate about research, I realised the need to contribute to addressing the pandemic. While my research focus was initially on cancer diagnostics and therapeutics, the closure of our laboratory forced us to adapt. We became more creative and shifted our strategy to bioinformatics and computational simulations to identify natural products that could target SARS-CoV-2. This shift in research direction resulted in several publications and collaborations with scientists from Europe and Asia. When mRNA vaccines became available, the research group I led, consisting of medical students and physicians, was among the first to investigate the immune response heterogeneity in individuals vaccinated with SARS-CoV-2 mRNA vaccines.

The pandemic profoundly changed the trajectory of my research, pushing me to adapt, collaborate internationally, and explore new avenues of study. It underscored the importance of innovative approaches, efficient vaccination strategies, and understanding the long-term effects of COVID-19. Through our research, we hope to contribute to the global efforts in combating the pandemic and improving public health outcomes.

I also had the opportunity of working under Dr. Heba Mostafa at the Johns Hopkins Hospital. Using next-generation sequencing, I tracked the prevalence of R346 substitution mutation among SARS-CoV-2 Omicron subvariants.

In her lab, I investigated the implications of this substitution mutation in the spike receptor binding domain of the virus in patient outcomes, including hospitalisation rates, mortality, the development of severe COVID-19 disease, and the need for intensive care and oxygen supplementation.

Beta HPV Vaccine

In the meantime, I am turning my attention back to other viruses. Cervical cancer, primarily caused by alpha HPV types, remains a significant health burden for women. The currently available vaccines target these alpha HPV types by utilising virus-like particles of the L1 capsid protein. However, there are also beta HPV types that typically cause benign skin lesions but can lead to malignant transformation in immunocompromised individuals and those with epidermodysplasia verruciformis, potentially resulting in cutaneous squamous cell carcinoma. Unfortunately, the existing vaccines do not provide protection against beta HPV types.

Our lab led by Professor Richard Roden has been actively involved in the development of adeno-associated virus-like particles (AAVLP) as a vaccine platform using HPV L2 capsid instead of L1. This platform aims to target both alpha and beta HPV types. In my research, I demonstrated that an adjuvanted AAVLP HPV16/31 L2-based vaccine candidate generates L2-specific antibodies that are broadly cross-reactive to both alpha and beta HPV types within two weeks of immunisation. Furthermore, we also observed sustained humoral immune protection against HPV16 in mice three months post-immunisation.

Currently, a human clinical trial is underway to facilitate the translational application of this vaccine platform in combating diverse HPV types that cause both cutaneous and mucosal cancers. The goal is to develop an effective and comprehensive solution to address the medical challenges posed by cancer-causing HPV.

#LINO23 – Stage for Collaborations

I am eagerly looking forward to the highly anticipated 72^nd Lindau Nobel Laureate Meeting in Physiology/Medicine, recognising its immense potential for providing invaluable experiences and remarkable opportunities. As an aspiring participant, I am excited about the prospect of connecting with visionary scientists and accomplished delegates from across the globe, fostering collaboration and facilitating the exchange of knowledge and ideas.

The 72^nd Lindau Nobel Laureate Meeting offers a unique and enriching environment for networking and interaction with delegates representing diverse backgrounds and cultures. Engaging in stimulating discussions with exceptional individuals will not only broaden my awareness of different societies but also provide space for personal and professional development.

For quite some time, I have nurtured a strong aspiration to attend the Lindau Nobel Laureate Meeting due to its renowned interdisciplinary approach to learning and discovery. The convergence of minds from various disciplines sets the stage for a fertile ground of collaborative problem-solving, particularly in tackling pressing challenges such as emerging infectious diseases, antimicrobial resistance, and vaccine hesitancy.