Budding Research Projects at Phil-DIAMOND

Budding Research Projects at Phil-DIAMOND

November 06, 2021

By: Isabella Orteza, UPCM 2025

A stimulating three-year program funded by the Department of Science and Technology-Philippine Council for Health Research and Development (DOST-PCHRD) was recently started in January 2021 but is already quickly executing innovative studies to keep an eye on.

Thanks to a recent interview with the program leader Dr. Marissa Marcelo Alejandria and her co-investigators Dr. Christian Francisco and Dr. Ana Joy Padua, further information on the program’s creation, current progress, and future plans are detailed in this article.

The Phil-DIAMOND or the Philippine Program for Diagnostic Biomarkers, Disease Modeling and Nutraceutical Product Development: Initial Focus on HIV-related Neurocognitive and Metabolic Complications was born out of UP’s ongoing collaboration with the Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii in Manoa, and University of St. Louis in Missouri. With the funding of the DOST-PCHRD, the program was able to send Dr. Alejandria’s research mentees and current co-investigators Dr. Francisco and Dr. Padua abroad to bring their knowledge back home and establish research projects that have relevance in our society.

The main goal of this program is to address the growing needs of fellow Filipino people living with HIV (PLHIV). As Filipinos have been receiving effective antiretroviral therapy (ART) through different treatment hubs, the program’s researchers anticipate that Filipino PLHIV will eventually manifest different sets of HIV-related complications called serious non-AIDS defining events (SNAEs), especially since the pathogenesis of the disease evolves with highly effective treatment regimens. These SNAEs include non-AIDS malignancies, HIV-associated neurocognitive disorder, cardiovascular events, renal and hepatic disease, bone disorders, and other metabolic disorders. Through this program, the researchers aim to identify possible immune biomarkers for the early diagnosis of SNAEs and to discover therapeutic targets for adjunct interventions to ART.

The Phil-DIAMOND’s objectives from its three component projects are to identify inflammatory traits (biomarkers) associated with HIV in relation to the virus’ neurocognitive and metabolic complications among Filipino patients, to study critical molecular processes involving these biomarkers through disease models, and to develop probiotic-based nutraceutical products which can serve as adjunct therapy for HIV-related complications.

Project 1, led by Dr. Alejandria with Dr. Christian Francisco and MD-PhD graduate Dr. Ana Joy Padua, will characterize immune cells for HIV-related biomarkers and perform clinical assessments of Filipino HIV patients. Project 2, led by Dr. Ahmad Mazahery of the UPD Institute of Biology with Dr. Mylah Villacorte-Tabelin and MD-PhD graduate Dr. Sheriah Laine de Paz-Silava, will generate biological models that mimic symptoms of HIV complications to provide pre-clinical molecular data that cannot be obtained from patient-level studies. Lastly, Project 3, led by Dr. Marilen Balolong of the UPM College of Arts and Sciences with Dr. Francisco Elegado and MD-PhD Program Coordinator Dr. Leslie Dalmacio, will screen novel probiotic strains for the development of functional food products that can be used as adjunct therapy for HIV-related complications.

[In the photo: Dr. Ana Joy Padua] The UP Manila Flow Cytometry Core opens up groundbreaking avenues for local research in understanding the dynamics of HIV and the immune system among Filipino patients. Photo from Dr. Marissa Marcelo Alejandria.

Discussing the implications and relevance of Project 1, Dr. Alejandria and her co-investigators explained, “HIV infection is now a chronic disease thanks to the wide use of ART. However, HIV is not fully eradicated in the body and stays in various reservoir sites like the brain, bone marrow, and lymph nodes to name a few. This viral persistence causes the continuous immune activation that will later lead to immune senescence and exhaustion. These processes are associated with various HIV-related chronic complications like dementia and cardiometabolic complications. The characterization of immune cells will be done by measuring the expression of various immune receptor markers and ligands using flow cytometry in a process that is called immunophenotyping.

“With this program, we received support from the DOST-PCHRD to establish here in our university the UP Manila Flow Cytometry Core composed of a 19-color cell analyzer and a 15-color cell sorter. Now that we locally have a flow cytometry facility, we will be able to characterize these immune markers that will help us understand the dynamics of HIV and the immune system among Filipino patients. There is also a chance to look for markers (receptors and ligands on immune cells) that can be used as a potential target for therapy to prevent, attenuate, and possibly treat chronic complications from HIV infection.”

Dr. Christian Francisco, along with his co-investigators, fly to Hawaii Center for AIDS at the University of Hawaii to learn new ways to revamp our local HIV research scene. Photo from Dr. Marissa Marcelo Alejandria

Along with the program’s aim to identify biomarkers and potential targets for therapy, the program also aims to find therapeutic agents in the form of probiotics. “The use of probiotics as adjunct therapy for HIV-associated gut dysbiosis and gut microbial translocation is still in the early or investigative stage. However, since ART alone cannot effectively control these events, we think that a possible adjunct therapy targeting the gut microbiota to curb gastrointestinal inflammation is necessary. Probiotics and prebiotics could help support and grow the microbiota. Through this project, we aim to develop locally-sourced probiotic strains that will provide possible preclinical data on adjunctive therapy for HIV.”

Besides the exciting research that all students and faculty will now be looking forward to, the program also led to the establishment of a local flow cytometry core and a virology laboratory. Dr. Alejandria added that, “the virology laboratory is currently hosted at the UP College of Public Health and is most definitely open to all researchers interested in virology research, whether on HIV or other viral infections. It is equipped with two biosafety level 2 cabinets and various equipment for cell culture studies (CO2 incubator, liquid nitrogen tanks, -80°C freezer, refrigerated centrifuges, cell counters, microscopes, etc.). Anyone who is interested in performing virology study techniques, from beginners to veterans, are all welcome to collaborate in our lab.”

The Phil-DIAMOND project headed by program leader Dr. Marissa Marcelo Alejandria (4th from the right, wearing purple in 2nd picture)​​, with their international collaborators, hopes to usher in a new age of medical research to address the growing needs of Filipino people living with HIV. Photo from Dr. Marissa Marcelo Alejandria.

Lastly, in relation to the program’s plans for the future, the researchers shared with excitement that, “we most definitely plan to continue what we have started in Phil-DIAMOND. Once we have characterized the immune response among our Filipino PLHIV, we plan to further improve these candidate biomarkers to develop an immune marker panel for the diagnosis of HIV-related complications. For the in vitro disease modeling of HIV, we plan to test other candidate drugs for high-throughput testing. We plan to test the locally isolated probiotics in vivo in animal models and in humans. Also, we already have at least two other projects from UP Manila and UP Diliman who will use our UPM flow cytometry core facility.”

As can be seen through the compelling projects of the Phil-DIAMOND, the program is leading our society towards a progressive future in terms of facilitating early diagnoses and discovering innovative adjuvant therapies for Filipino PLHIV. Along with the aforementioned projects, the program brings in new equipment for research such as flow cytometers and a virology laboratory to the UP College of Public Health. With the advent of new research, equipment, and laboratories, the College is now set to usher in a whole new era for medical research and collaborations for all students and faculty to look forward to.