Congratulations Dr. Marcos Ramos-Benitez!

We congratulate Dr. Marcos Ramos-Benitez on receiving the 2024 National Institute of Health Director's Award. This award was presented for his efforts as a member of the NIH COVID-19 Autopsy Team, nominated by the NIH Clinical Center.

Novel Inhibition of Central Carbon Metabolism Pathways by Rac and CDC42 inhibitor MBQ167 and Paclitaxel

Abstract

Triple negative breast cancer (TNBC) represents a therapeutic challenge where standard chemotherapy is limited to paclitaxel. MBQ-167, a clinical stage small molecule inhibitor that targets Rac and Cdc42, inhibits tumor growth and metastasis in mouse models of TNBC. Herein, we investigated the efficacy of MBQ-167 in combination with paclitaxel in TNBC pre-clinical models, as a prelude to safety trials of this combination in advanced breast cancer patients. Individual MBQ-167 or combination therapy with paclitaxel was more effective at reducing TNBC cell viability and increasing apoptosis compared to paclitaxel alone. In orthotopic mouse models of human TNBC (MDA-MB-231 and MDA-MB-468), individual MBQ-167, paclitaxel, or the combination reduced mammary tumor growth with similar efficacy, with no apparent liver toxicity. However, paclitaxel single agent treatment significantly increased lung metastasis, while MBQ-167, single or combined, reduced lung metastasis. In the syngeneic 4T1/BALB/c model, combined MBQ-167 and paclitaxel decreased established lung metastases by ~80%. To determine the molecular basis for the improved efficacy of the combined treatment on metastasis, 4T1 tumor extracts from BALB/c mice treated with MBQ-167, paclitaxel, or the combination were subjected to transcriptomic analysis. Gene set enrichment identified specific downregulation of central carbon metabolic pathways by the combination of MBQ-167 and Paclitaxel but not individual compounds. Biochemical validation, by immunoblotting and metabolic Seahorse analysis, shows that combined MBQ-167 and paclitaxel reduces glycolysis. This study provides a strong rationale for the clinical testing of MBQ-167 in combination with paclitaxel as a potential therapeutic for TNBC and identifies a unique mechanism of action.

Publications:

Pubmed

AACR Journals

The Microbiology Department proudly shares a manuscript just published in Cancers by the Dorta Lab, focusing on identifying immune and microbial biomarkers associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer.

MDPI website: https://www.mdpi.com/2072-6694/16/11/2065

The first author, Miss Jennifer Diaz, is a PhD candidate of Dr. Dorta who has focused her work on the topic of host-microbe response to anti-PD-1 immunotherapy in preclinical models of oropharyngeal carcinoma. We also congratulate Mr. Michael Rodriguez, an MS candidate in the Dorta lab who will continue working towards a PhD degree.

PR-INBRE

Dear all:

We thank the support of the U54 IMPACT and its leadership both at UPR and MDACC. We also thank additional support by at UPR by RISE R25 GM061838;  RCMI U54MD007600 and PR-INBRE 5P20GM103475; and at MDACC: P30CA01667; F31CA228207; R01CA256006; P50CA127001.

Congrats to the team, to many more!

Click here to see the publication at MDPI website.

Cervical cancer (CC) is women’s fourth most common cancer worldwide. A worrying increase in CC rates in Hispanics suggests that besides Human papillomavirus infections, there may be other cofactors included in the epithelial microenvironment that could play a role in promoting the disease. We hypothesized that the cervical microbiome and the epithelial microenvironment favoring inflammation is conducive to disease progression in a group of Hispanics attending gynecology clinics in Puerto Rico. Few studies have focused on the joint microbiota and cytokine profile response in Hispanics outside the US, especially regarding the development of precancerous lesions. We aimed to investigate the relationship between the cervicovaginal microbiome and inflammation in Hispanic women living in PR while considering cervical dysplasia and HPV genotype risk. Cervical samples collected from 91 participants coming to gynecology clinics in San Juan, underwent 16S rRNA genes (V4 region) profiling, and cytokines were measured using Luminex MAGPIX technology.
Cytokines were grouped as inflammatory (IL-1β, TNFα, IFNγ, IL-6), anti-inflammatory (IL- 4, IL-10, TGFβ1), and traffic-associated (IL-8, MIP1a, MCP1, IP10). They were related to microbes via an inflammation scoring index based on the quartile and tercile distribution of the cytokine’s concentration. We found significant differences in the diversity and composition of the microbiota according to HPV type according to carcinogenic risk, cervical disease, and cytokine abundance. Community State Types (CSTs) represents a profile of microbial communities observed within the vaginal microbiome ecological niche, and Lactobacillus-depleted CST IV had ~ 90% dominance in participants with high-grade squamous intraepithelial lesions and high-risk HPV. The increasing concentration of pro-inflammatory
cytokines was associated with a decrease in L. crispatus. In contrast, dysbiosis-associated bacteria such as Gardnerella, Prevotella, Atopobium concomitantly increased with pro-inflammatory cytokines. Our study highlights that the cervical microbiota of Hispanics living in Puerto Rico is composed mostly of diverse CST profiles with decreased Lactobacillus and
is associated with a higher pro-inflammatory environment. The joint host-microbe interactionanalyses via cytokine and microbiota profiling have very good translational potential.

PLOS ONE link: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0284673

SEIDeA23 Awards

Congratulations to our exceptional students for their outstanding achievements and well-deserved awards in the recent SEIDeA23 meeting! Your dedication, perseverance, and remarkable talents have not only elevated your individual profiles but have also enriched our entire community. Your accomplishments serve as an inspiration to us all, and we look forward to witnessing your continued success in the future. Well done!

On March 31 2023, the Vice Presidency for Research and Innovation of the University of Puerto Rico and latinasteam.com recognized the scientific contributions of Doctors Emma Fernandez Repollet and Filipa Godoy-Vitorino in a ceremony in Rio Piedras, entitled “Symposium the Power of Women in the Science", celebrating the trajectory of outstanding women in science, technology, engineering, art and mathematics (STEAM) from the 11 campuses of the UPR.

We congratulate Dr. Filipa Godoy for receiving recognition as “Best INBRE Presentation" in her session by the NISBRE 2022 Organizing Committee. This symposium hosted a competitive field of distinguished young INBRE, COBRE, and CTR investigators selected among all 24 IDeA states to be presenters.  We therefore wish to congratulate all the oral presenters as well as our virtual poster presenters at this symposium for their outstanding presentations. Winners in other sessions and categories are listed below.

NISBRE 2022 Presentation Winners

PR-INBRE postdoc Dr. Ailed Cruz-Collazo won best poster at the PRSTRT Forward Symposium

The INBRE postdoc Dr. Ailed Cruz-Collazo won best poster at the PRSTRT Forward Symposium for her poster titled: “Pre-clinical efficacy of the Rac/Cdc42 inhibitor MBQ-167 in combination therapy with Paclitaxel.” Authors: Ailed M. Cruz-Collazo¹, Olga Katsara², Elizabeth Salvo², Jean Ruiz¹, Robert J Schneider², and Suranganie Dharmawardhane^1,3

Best Poster Presentation SACNAS 2022

Congrats to Travis Santana Lopez, Dr. Natasha De León student! Travis was recipient of the SACNAS 2022 best poster presentation (Title: Insights into the health risk imposed by bacteria associated with Saharan dust events through the understanding of the pathogenic pathways and antibiotic resistance genes.) for life sciences 2022!

Congratulations Dr. Suranganie Dharmawardhane

We congratulate Dr. Suranganie Dharmawardhane, PR-INBRE Program Coordinator, for her new DoD grant award on “Translational Development of MBQ-167 as Targeted Therapy for Metastatic Breast Cancer”.

TECHNOLOGY TRANSFER AWARD

The Puerto Rico INBRE Program congratulates Dr. Beatriz Zayas who has been awarded a grant from the EnTRUST Program of the Puerto Rico Science, Technology and Research Trust Technology Transfer Office.