GRC Newsletter

GRC Highlights
In a new study published this month, researchers from the GRC mapped, for the first time, both the regional distribution and the interlobular and intralobular patterns of fat deposition across 100 human donor pancreases—the largest histologic study of its kind. Read it here (external link)

Using blinded histologic analysis, the team quantified fat separately in the head and tail of the pancreas and within the interlobular and intralobular compartments. The study showed that pancreatic fat is not distributed uniformly across the gland. Female sex was consistently associated with greater fat deposition across the measured regions and compartments, while tail intralobular fat was greater than that observed in the pancreatic head.

The study identified distinct metabolic associations according to anatomical location. Obesity was most strongly associated with interlobular fat in the pancreatic head, whereas type 2 diabetes was associated with intralobular fat in the pancreatic tail.

These findings suggest that pancreatic fat represents a heterogeneous process and that measurements obtained from a single region may not fully characterize fat deposition across the organ. The results provide an anatomical and histological framework for future studies examining how regional pancreatic fat relates to metabolic dysfunction, pancreatitis, diabetes, and pancreatic cancer.

This work is particularly timely in light of a recent landmark international consensus published in Nature Reviews Gastroenterology & Hepatology, which included Dr. Bishehsari of the Gastroenterology Research Center (GRC) among its expert contributors. The consensus establishes a standardized framework for pancreatic fat research, distinguishing intrapancreatic fat deposition as a measurable morphologic feature from fatty pancreas disorder, a condition in which excess pancreatic fat is associated with adverse health outcomes. Together, the consensus and the GRC study help advance a more consistent approach to terminology, fat assessment, and understanding the clinical implications of pancreatic fat accumulation.

Post-Doc Highlight
GRC postdoctoral research fellow, Luca Santovito, MD, was invited to join the Innovative Drug Discovery and Development Scholars Steering Committee (IDDD), on behalf of the Gulf Coast Consortia (GCC).

Luca will be representing our institution and the GRC while collaborating with fellow student and postdoctoral representatives from across the consortium.

The Gulf Coast Consortium (GCC) is a collaborative alliance of major universities and research institutions in the Texas Medical Center and Gulf Coast region.

The Institute for Drug Discovery and Development (IDDD) is one of the GCC’s key programs. Established to accelerate the translation of scientific discoveries into new therapies, the IDDD provides expertise, resources, and collaborative support for drug discovery, development, and commercialization. The institute helps researchers move promising laboratory findings toward clinical application by offering services such as drug screening, medicinal chemistry support, project development, industry partnerships, and entrepreneurial training.

Paper Highlights of the Month!

A tumour-derived organoid biobank maps cancer gene dependencies (external link)

Patient-Derived Organoids Advance Precision Oncology a new study published in Nature established a biobank of 256 patient-derived tumor organoids spanning colorectal, pancreatic, gastric, esophageal and ovarian cancers.

Multi-omic characterization and genome-wide CRISPR screening identified tumor-specific gene dependencies and therapeutic vulnerabilities, highlighting the growing role of organoid platforms in translating patient tumor biology into precision oncology.

These advances closely parallel research at the Gastroenterology Research Center (GRC), where investigators leverage patient-derived organoids and organ-on-chip technologies to model gastrointestinal disease and investigate how circadian rhythms influence cancer initiation, progression, and treatment response. By integrating physiologically relevant tissue models with microengineered systems that recapitulate the intestinal microenvironment, GRC researchers are developing translational platforms that bridge fundamental discovery and clinical application, accelerating the identification of predictive biomarkers, optimizing therapeutic timing and efficacy, and advancing personalized treatment strategies for gastrointestinal diseases and cancer.

Click here for more of the GRC’s research

GRC member Dr. Pooja Shivshankar, PhD, MCHC, was selected to serve as an Early Career Reviewer for NIH study sections focused on Immunity and Autoimmune Diseases (AI, III, MAI).

In this role, she participated in the peer review of NIH grant applications, evaluating their scientific merit, innovation, significance, and potential impact. Selection for the NIH Early Career Reviewer program recognizes emerging scientific leadership and provides investigators with an opportunity to contribute to the NIH peer-review process while gaining valuable insight into the evaluation of biomedical research proposals.

We congratulate Dr. Shivshankar on this professional achievement.

Issue 10 – July 2026

As summer comes to a close, the Gastroenterology Research Center (GRC) bids farewell to its talented cohort of summer students. This year, the GRC welcomed undergraduate students from Rice University and the University of Houston, all of whom aspire to pursue careers in medicine.

Throughout their time at the GRC, Gloria Huang from Rice University, and Ayaan Ansari, and Sasha Prudsky from the University of Houston, gained valuable hands-on research experience, participating in laboratory activities such as DNA and RNA extraction, organoid maintenance, and other essential techniques that support the center’s ongoing research studies.

We also congratulate our own Jessica Wang as she embarks on the next chapter of her professional journey at Baylor College of Medicine. Jessica joined the GRC in 2025 from Pediatric Gastroenterology and initially served as a Research Assistant in the laboratory. Over the past eight months, she transitioned into a Research Coordinator role, where she played a vital part in recruiting participants for the GRC’s numerous research studies.

She also developed expertise in IRB processes, regulatory compliance, and protocol development.

Jessica hopes to follow in the footsteps of her mentors and pursue gastroenterology.

We wish Jessica the best of luck in her journey and hope to welcome Dr. Wang back to the world of GI in the future.

In June, Dr. Faraz Bishehsari was invited to present at SLEEP 2026, the annual meeting of the Associated Professional Sleep Societies (APSS), a joint initiative of the American Academy of Sleep Medicine (AASM) and the Sleep Research Society (SRS). As the largest multidisciplinary sleep medicine and sleep research conference in North America, SLEEP brings together leading investigators and clinicians from diverse fields, including circadian biology, neuroscience, pulmonology, psychology, pediatric sleep medicine, and related disciplines. Dr. Bishehsari presented “Circadian Disruption, Sleep, and the Gut Microbiome: Novel Chronotherapeutic Strategies for Metabolic Health.”

This symposium examined how circadian disruption from shift work, sleep deprivation, and irregular eating patterns triggers gut microbiota dysbiosis, creating a bidirectional feedback loop that drives metabolic disease through inflammation, hormonal dysregulation, and impaired energy homeostasis.

Circadian rhythms regulate metabolism, endocrine and immune function, and behavior through a central brain clock and peripheral clocks throughout the body. The gut microbiota also follows daily rhythms that are closely linked to host circadian mechanisms. Disruption of this circadian-microbial synchrony by shift work, sleep loss, or irregular eating can promote dysbiosis, inflammation, metabolic dysfunction, and disease risk. Insufficient sleep and circadian misalignment predispose individuals to poor metabolic health and promote weight gain, with millions of individuals worldwide not obtaining sufficient sleep for healthy metabolic function. Circadian misalignment, such as from shift work, is linked to a 23-25% higher risk of obesity and central adiposity. Insomnia and other sleep disorders can disrupt the gut-brain axis by altering the gut microbiota, reducing microbial diversity and beneficial metabolite-producing bacteria. This bidirectional relationship creates a vicious cycle in which circadian disruption worsens microbial imbalance, further impairing sleep and metabolic health.

Paper Highlights of the Month!

The GRC team recently collaborated on the interdisciplinary study, Multi-Omics Analysis Defines Endotypes and Systemic Inflammation in Primary Ciliary Dyskinesia: A Comparison with Healthy Controls (external link).

In collaboration with UT Pediatric Pulmonology and led by Dr. Ricardo Mosquera, Medical Director of the UT Physicians High Risk Children’s Clinic at McGovern Medical School at UTHealth, the study revealed that even clinically stable patients with primary ciliary dyskinesia (PCD) exhibit persistent systemic immune activation detectable through a simple cheek swab. The findings further demonstrated that patients with microtubular defects and those older than 10 years showed the strongest inflammatory signatures, suggesting progressive systemic immune dysregulation beyond impaired airway clearance alone.

Microbiome analyses led by the GRC team revealed distinct oral microbial communities in PCD patients, characterized by enrichment of opportunistic pathogens and altered microbeimmune interactions compared with healthy controls. PCD is a systemic inflammatory disease with distinct endotypes, supporting personalized anti-inflammatory therapies and noninvasive longitudinal monitoring, particularly in young children.

The GRC recently published a collaborative study, Prebiotic intervention changes host and microbe proteomes in plasma extracellular vesicles of Parkinson’s disease (external link)

In this study, researchers demonstrated that a precision prebiotic intervention can modify both host and microbial protein signatures in plasma extracellular vesicles
(EVs) of patients with Parkinson’s disease (PD). Building on a prior clinical trial showing improvements in gut dysbiosis and PD symptoms, the team found that EV proteomic profiles not only distinguished PD patients from healthy controls but also correlated with disease severity. Importantly, prebiotic treatment shifted both host and microbial EV signatures toward a healthier profile, highlighting the dynamic interplay of the microbiota-gut-brain axis. Using a combined host-microbe proteomic signature, the investigators were able to accurately classify PD status and stratify disease severity, underscoring the potential of EV-based biomarkers for precision medicine.

These findings support plasma EV proteomics as a promising, noninvasive platform for monitoring biological responses to microbiome-targeted therapies and for developing future diagnostic and disease-staging biomarkers in PD.

Dr. Pooja Shivshankar of the GRC recently published a systems biology study examining how microRNAs and genetic variants in 3′ untranslated regions may regulate the
complement system. The work identifies candidate miRNA-SNP interactions that could influence immune and inflammatory diseases, including inflammatory bowel disease, and provides targets for future functional studies.

Issue 9 – June 2026

In June, the GRC presented 3 posters at the 49th annual Research Society on Alcohol (RSA) Scientific Meeting in San Antonio, TX.

Dr. Xiangsheng Huang presented Alcohol and Feeding-Time Misalignment Reshape the Gut Microbiome to Promote Inflammaging.

Aging combined with irregular eating patterns disrupts gut circadian rhythms, promotes inflammation, and weakens the intestinal barrier, effects that are further exacerbated by alcohol. These changes are linked to microbiome disruption and reduced production of beneficial metabolites like SCFAs thereby contributing to the development and progression of inflammaging.

Dr. Wankun Deng’s poster was on the GRC’s AREK study; Microbial Enterotype in Alcohol-Related Organ Damage.

The study examines how alcohol exposure reshapes the gut microbiome and contributes to alcohol-related organ damage. Across mouse and human datasets, alcohol induces a reproducible microbial shift characterized by enrichment of pro-inflammatory taxa (e.g., Escherichia-Shigella) and depletion of beneficial Firmicutes. These microbiome changes are associated with inflammation, barrier dysfunction, and liver disease. The study establishes a scalable, multi-omics “AREK” framework to define alcohol-associated microbial enterotypes and identify biomarkers linked to disease risk and severity.

Dr. Connor Cheek presented a poster on Alcohol–Gut Microbiome–Cognition Links in an Elderly Population.

This study examines links between alcohol use, the gut microbiome, and cognitive function in older adults. Moderate alcohol use showed modest positive associations with cognition and shifts in gut microbial composition, including changes in butyrate-producing species. Overall, the findings suggest a complex and likely confounded relationship.

Moderate drinkers tend to have better cognition, likely not because of the alcohol intake, but because the drinking happens socially, and socializing with peers produces a strong positive effect on cognition that outweighs any effect of drinking.

The GRC team enjoyed dinner along the San Antonio Riverwalk with colleagues from RUSH University. The GRC participates in several collaborations with RUSH University, including our latest AREK study and our “Paper of the Month” for June.

Paper Highlight of the Month!

The GRC team recently collaborated wit h Rush University Medical Center, Illinois, Chicago.

Study Title: Prebiotic intervention changes host and microbe prot eomes in plasma extracellular vesicles of Parkinson’s disease (external link).

Can a 10-Day Fiber Supplement Shift the Biology of Parkinson’s Disease?
Can a blood test be used as a window into Gut-Brain axis?

This new proof-of-concept study by Sharma et al. published in Scientific Reports, from Rush University Medical Center offers a striking answer: “Possibly, Yes!”. And the molecular evidence is visible in the blood within days. Given the complexity of the PD diagnosis and the invasive sampling procedures like spinal taps, this study suggests that a relatively simple blood test analyzing tiny particles called extracellular vesicles (EVs) could change that picture, while also shedding light on how the gut microbiome contributes to PD.

Analysis of Plasma EVs from 20 PD patients and 10 healthy controls through high-resolution mass spectrometric proteomics analysis mapped 631 proteins across all samples, both human proteins and bacterial proteins from gut-derived EVs. The PD-EV proteins showed increased inflammatory MAPK signaling and dampened protective immune response.

The organic prebiotic fiber blend (with resistant starch, resistant maltodextrin, stabilized rice bran, and inulin) given to PD patients for just 10 days significantly reduced levels of lipopolysaccharide binding protein (LBP, a hallmark of the intestinal barrier dysfunction long suspected to drive neuroinflammation in PD. In contrast, it increased levels of anti-inflammatory proteins like ANK1, APOB, and SPTA1, which had been abnormally low in PD participants, while reducing pro-inflammatory markers like CD9 and IGHG4.

In both mild and moderate PD groups, the prebiotic intervention also dialed down a key pro-inflammatory Fc γR1 immune signaling and modulated complement associated pathways, suggesting that prebiotic-induced changes in the gut microbiome may influence systemic immune and inflammatory processes implicated in Parkinson’s disease.

Dr. Bishehsari was featured in a leadership article for the UK Biobank, offering expert insight on the study examining regular pharmaceutical opioid use and cancer risk through prospective cohort and Mendelian randomization analyses.

Issue 8 – May 2026

The GRC has had a busy month of May with several conferences attended by our team!

Our Post-Doc Luca Santovito presented at the 7th Annual GCC Innovative Drug Discovery and Development Conference at Rice University (external link). His abstract, Decoding Tumor-Specific Circadian Profiles for Personalized Chronotherapy in Cancer, explains how many genes, including those in pancreatic tissue, exhibit oscillatory expression patterns aligned with the circadian cycle.

Chronotherapy leverages this principle by timing drug administration to coincide with these rhythms, aiming to optimize efficacy. While clinical trials in cancer chronotherapy have shown time-dependent variations in drug response, results remain inconsistent—likely due to simplistic patient randomization into morning versus evening dosing. We hypothesize that tumor-specific molecular alterations create unique circadian signatures, requiring individualized approaches.

Pancreatic ductal adenocarcinoma (PDA), among the deadliest cancers and projected to become the second-leading cause of cancer-related death in the US by 2030, exemplifies this need. Personalized medicine strategies typically rely on large tissue samples, yet most PDA patients do not undergo upfront surgery, limiting access for molecular profiling. To overcome this, we use patient-derived organoids (PDOs) from routine biopsy samples. Organoids recapitulate tissue phenotype and correlate with clinical drug response, offering a unique platform for personalized chronotherapeutics.

The GRC also presented their study on Alcohol and Feeding-Time Misalignment Reshape the Microbiome to Promote Inflammaging at The Society for Research on Biological Rhythm (external link) conference in Florida.

The study follows how chronic low-grade inflammation coupled with epithelial barrier dysfunction, collectively termed inflammaging, characterizes age-related intestinal vulnerability and predisposes to disease. Circadian disruption from irregular eating habits and alcohol exposure, both prevalent lifestyle factors, independently promote gut inflammation through barrier leakage microbial dysbiosis, and loss of metabolic regulation. However, their synergistic interactions with aging remain undefined, particularly how they dismantle host-microbiome temporal coordination to drive inflammaging.

Aging and feeding-time misalignment prime the colon for alcohol-mediated inflammaging through circadian-microbiome uncoupling, SCFA depletion, and barrier disruption. Alcohol exerts dominant, multi-pathway disruption, while rhythmic SCFA-producers are suggested to act as peripheral zeitgebers capable of rescuing epithelial homeostasis independently of central clocks.

Modeling Patient-Derived Pancreatic Organoid for Precision Chronotherapy in PDAC
Luca Santovito, MD, – Postgraduate Research Fellow UT Health Houston Laboratory of Dr. Faraz Bishehsari, MD, PhD.

Luca was also invited to present at the TMC 2nd annual Organoid Day.

The GRC’s Organoid study shows how we leverage patient-derived organoids (PDOs) from routine biopsy samples and from healthy pancreases from donors. Healthy pancreas organoids recapitulate tissue phenotype and correlate with clinical drug response, while PDOs preserve patient-specific molecular and phenotypic characteristics that enable modeling of disease progression and drug sensitivity, offering a unique platform for personalized chronotherapeutics.

Dr. Bishehsari presented “Circadian Rhythms and the Gut Microbiome in Aging and GI cancer” at RUSH Universities Provost’s Research Seminar Series in Chicago.

The McGovern Medical School Scoop on the GRC!

The Gastroenterology Research Center developed a “tumor-on-a-chip” system designed to recreate that environment outside the human body, offering a more realistic way to study the disease and evaluate treatments.

Paper Highlight of the Month!

The GRC team recently published an article in the journal Immune Network, from Korean Association of Immunologists, a sister organization of American Association of Immunologists (AAI).

Title: Complement Anaphylatoxin C5a-Induced Mouse Lymphatic Functions Modulate Interactions Between Endothelial Cells and T Lymphocytes (external link).

The GRC has published an article in the April 2026. Our newly appointed Assistant Professor Dr. Pooja Shivshankar, PhD, in GRC has published a research article, as the corresponding author. The study proposes a mechanistic chain: complement activation→C5a/C5ar1 on lymphatic endothelial cells → iNOS induction via JAK3/STAT3→lymphatic dilation and reduced propulsion → accumulation of activated Th1 cells in lymph nodes→CD146/vimentinmediated transmigration of Th1 cells into systemic circulation. The authors frame this axis as a potential contributor to chronic inflammatory diseases, including autoimmunity and lymphedema, where aberrant complement activation and impaired lymphatic function co-occur. Acute intradermal C5a challenge in wildtype mice reduced lymphatic propulsion from ~7–9 to ~3–4 pulses per minute, an effect absent in C5ar1-knockout mice and rescued by the selective iNOS inhibitor L-NIL, implicating endothelial iNOS-induced downstream of C5ar1 via JAK3/STAT3 signaling, as the mechanistic driver of lymphatic vessel dilation and flow impairment.

Using co-immunoprecipitation and mass spectrometry, the authors further identify a novel CD146-vimentin interaction between endothelial cells and T cells that facilitates Th1 activation and transmigration, independent of changes in T cell proliferation.

These findings have led Dr. Shivshankar to envisage aberrant complement activation to systemic Th1-driven inflammation, with potential relevance to the molecular pathogenesis of inflammatory bowel disease (IBD) in inflammaging with her current role in GRC.

Dr. Haydn E. Rich, MD is the first author, who worked under the supervision of Dr. Shivshankar for three years as research elective course during her MD program at UTHealth-McGovern Medical School.

Issue 7 – April 2026

Faculty Highlight: Congratulations Dr. Huang!

Dr. Xiangsheng Huang was a recipient of the 2026 DDC Pilot Award for the project entitled “Microbiome-Circadian Interactions in Inflammaging”. Dr Huang is the only UT internal medicine recipient of this award in over 10 years. The Texas Medical Center Digestive Diseases Center provides support to pilot/feasibility (P/F) projects in the area of GI-related research each year.

These funds specifically support projects related to the theme for the DDC.

This project investigates how lifestyle-driven circadian disruption and alcohol exposure reshape the gut microbiome to drive intestinal barrier dysfunction and promote age-related chronic inflammation (“inflammaging”). Using human microbiome data integrated with germ-free mouse models, the study will define microbiome–clock interactions that increase vulnerability to alcohol induced injury and identify microbiome-targeted strategies to restore barrier integrity, dampen inflammation, and support healthy aging.

Student Highlight:

Two of our students from Rice University, Priya Verma and Kate Chin, presented at Rice’s Natural Sciences Undergraduate Research Symposium.

Their presentation summarized the work they have done over the last 16 months on the project:

Gemcitabine Chronotherapy in PDAC Cell lines. The results show that:

• Gemcitabine has a significant killing effect in PDAC (expected — this is the main first line chemotherapeutic treatment used for this cancer), with differential inhibitory concentrations for different cell lines, as measured by IC50 cell viability assay.
• Dexamethasone is an effective method for synchronizing the circadian rhythm of PDAC cancer cells, as measured by qPCR of key clock genes.
• Gemcitabine administration may have differential effects on apoptosis in PDAC cell lines, dependent on their movement through their circadian rhythms, based on our overnight work and flow cytometry.

Dr. Faraz Bishehsari was invited to speak at the international Personalized Cancer Chronotherapy (PERCC) Network Meeting held this month in Paris.

There he presented his research on circadian biology and cancer treatment. The meeting brought together investigators across disciplines focused on advancing chronotherapy in oncology. Dr. Bishehsari emphasized the growing momentum in the field, citing discussions on chrono-immunotherapy, circadian biomarkers, and clock-targeted therapies. He shared his view of moving beyond simplified random assignment of morning vs. evening dosing paradigms toward more personalized chronotherapy strategies. By leveraging patient-derived organoids, we are beginning to uncover tumor-specific circadian programs that may guide individualized treatment timing and improve therapeutic response. The meeting represented a shared commitment to translating circadian biology into clinically meaningful advances for patients.

Dr. Bishehsari had the pleasure of being invited to speak at the Wound Healing Society meeting in Charlotte, NC last week.

His talk was on circadian rhythm regulation and gut barrier function. He presented in the session Clocking in for Tissue Health with a talk titled Timing Your Way to Better Barriers.

Paper Highlight of the Month!

The GRC team recently published an article in the journal Biofabrication. A journal of International Society of Biofabrication (ISBF).

Study Title: Biomechanical 3D tumor models on a micromilled high-throughput force sensor array (external link)

The GRC in collaboration with the team at University of Illinois, led by Dr. Saif, published on a high-throughput 3D tumor modeling platform that combines patient-derived pancreatic cancer constructs with an integrated biomechanical sensor array, fabricated affordably using micro-milled polymethylmethacrylate (PMMA) molds rather than conventional photolithography. The system simultaneously measures cellular contractile force and ECM stiffness across 16 parallel tumor constructs in a single dish, enabling mechanobiological readouts that standard viability assays cannot capture. Using co-cultures of MIA PaCa-2 cancer cells and pancreatic stellate cells. embedded in collagen I, the authors show that stromal cells rapidly stiffen the matrix twofold within 24 hours, recapitulating the desmoplastic microenvironment of pancreatic ductal adenocarcinoma.

Drug testing with Gemcitabine and the investigational stromal agent all-trans retinoic acid (ATRA) outperformed either drug alone across biochemical and biomechanical endpoints: viability dropped by ~13.5% in 3D constructs, epithelial apoptosis rose from 27.8% to 62.6% in patient-derived organoid co-cultures, and ECM stiffness was reduced by 50–60%, effects largely invisible in 2D culture. The platform’s ability to disentangle stromal from tumor cell contributions to drug resistance positions it as a promising tool for mechanobiology research and personalized cancer therapy screening.

The GRC contributed to a recent PNAS publication led by Dr. Changqing Ju, reflecting ongoing collaborations with investigators in other departments.

The paper investigates the role of eosinophils in inflammatory bowel disease (IBD), particularly through the enzyme cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2). The study finds that eosinophil-derived COX-2 is essential for protecting the intestinal barrier in colitis by promoting IL-22 production by type 3 innate lymphoid cells (ILC3s) via PGE2 signaling. Eosinophil-specific COX-2 deletion worsens colitis severity, while supplementation with recombinant IL-22 or a PGE2 analog reverses these effects. This research identifies an important eosinophil-ILC3 interaction and suggests therapeutic potential for targeting the eosinophil/PGE2/IL-22 axis in IBD.

Issue 6 – March 2026

GRC Director Faraz Bishehsari, MD, PhD, delivered an invited talk at the Stand Up To Cancer (SU2C) Innovation Summit on Approaches Toward Detecting and Treating Early-Onset Cancers, jointly organized by the American Association for Cancer Research and Stand Up To Cancer in February 2026. Dr. Bishehsari presented on Circadian Disruption: Emerging Risk Factor for Colorectal Cancer at the Stand Up To Cancer Innovation Summit. Bishehsari discussed how alcohol consumption, another risk factor for colorectal cancer, can synergize with circadian disruption to promote colon carcinogenesis in preclinical models. He then presented evidence from his human studies showing that late eaters had a higher prevalence of colon polyps, including advanced polyps, compared with non-late eaters. He also shared data from an unpublished human trial suggesting that alcohol consumption and abnormal eating times interact to disrupt central–peripheral
circadian synchrony, both in mice and in humans. When we eat or drink may be just as important as what we eat or drink, he concluded. The timing of eating is particularly important in younger individuals, who are at increased risk for early-onset colorectal cancer, in part because circadian misalignment is especially common in this age group. This research could help identify individuals at higher risk for colorectal cancer due to circadian rhythm disruption and could inform strategies for colorectal cancer prevention.

Dr. Faraz Bishehsari presented at High-Risk, High-Reward Research Symposium sponsored by The Common Fund at NIH in Bethesda, MD. In his presentation, entitled “Decoding Tumor-Specific Circadian Profiles for Personalized Chronotherapy in Cancer” Bishehsari demonstrated that pancreatic cancer is not biologically static over the course of the day. He showed that many genes in pancreatic ductal adenocarcinoma (PDA) follow clear time-of-day–dependent expression patterns, reflecting underlying circadian regulation. Importantly, these rhythms were not uniform across tumors. Using patient-derived organoids, he showed that it is possible to study circadian biology in tumors even when surgical specimens are unavailable. He presented data comparing different methods for synchronizing cellular clocks as the best match for the circadian patterns observed in native pancreatic tissue. Using this optimized approach, the team is circadian profiling pancreatic cancer and normal cells. Pathways central to tumor progression and drug resistance exhibit rhythmic behavior. Dr. Bishehsari and his team aim to capture patient-specific circadian signatures using scalable organoid models. Their findings so far support the idea that effective chronotherapy in pancreatic cancer will likely require individualized timing strategies, guided by tumor-specific molecular rhythms rather than fixed dosing windows.

Medical School Spotlight: The GRC was honored to be recognized in Dean Love’s inaugural Dean’s Dialogue, where its director, Dr. Faraz Bishehsari, was named among the top 10 funded researchers at McGovern Medical School.

Postdoc Spotlight: GRC post-doc, Luca Santovito, MD attended the CHARGE Conference in North Carolina to present Accelerated biological aging correlates with clinical outcomes and predicts organ damage in a population at high risk of chronic metabolic diseases. This collaborative study from GRC shows that biological age (BA), more than chronological age (CA), is linked to metabolic health. People aging faster (BA > CA) were more likely to have metabolic syndrome and related conditions. Higher BA was also associated with heart and liver damage, suggesting it could help identify at-risk individuals earlier.

Luca is also working on his PhD at the Maastricht University in Netherlands.

Dr. Atilla Ertan visits the GRC

In February, the GRC had the pleasure of welcoming Dr. Atilla Ertan for a tour of our lab and a brief chat about his life and work.

Dr. Faraz Bishehsari holds the Ertan Chair in gastroenterology research, a role that signifies both leadership in specialized gastrointestinal care and a commitment to training the next
generation of academic gastroenterologists. The position honors the legacy and standards established by the physician whose name it bears.

But who is Dr. Atilla Ertan?

Dr. Ertan’s path to becoming one of the most respected figures in gastroenterology began in Turkey, where he completed his medical degree at Ankara University. His early ambitions leaned toward a career in surgery, but that trajectory shifted during his medical school years. He credits the late Dr. Zafer Paykoc, a highly regarded professor known for shaping the fields of internal medicine and gastroenterology, with influencing his move toward GI medicine.

During his time at UPenn, Dr. Ertan trained under Dr. Frank Brooks, whom he describes as “one of the best GI physiologists at that time.” Under Dr. Brooks’ mentorship, he immersed himself in gastrointestinal physiology, focusing on GI peptides and their functions. His scientific curiosity later took him to Tulane University, where he worked alongside Professor Akira Arimura, celebrated for groundbreaking advances in neuroendocrinology, including the discovery of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP).

Over a career spanning more than half a century, Dr. Ertan has witnessed and contributed to the transformation of GI medicine. He often reflects on how far the field has come, recalling the early days when “the scopes were semi-rigid, and we were trained not to touch the pancreas, now we can get inside the pancreas and bile ducts!” The evolution of endoscopic diagnostics and therapy, he notes, stands among the most remarkable advancements he has seen. A defining part of his legacy has been his dedication to education, having trained hundreds of GI trainees who later advanced into academic leadership roles.

Today, even in retirement, Dr. Ertan remains active in the scientific community. Between extensive travels, he serves on advisory boards for three companies and continues to collaborate on
research initiatives with his teams, including ongoing communication with Dr. Bishehsari.

His message for the next generation of physicians and scientists is simple but urgent: “train yourself, daily biases, nonstop. GI is very advanced and if you don’t update yourself, you burn out easily. Prevent the burnout.”

Issue 5 – February 2026

Paper Highlight of the Month!

The GRC team recently published an article in the Wiley Advanced Science journal’s January issue.

A Patient-Derived Organ-on-Chip Platform for Modeling the Tumor Microenvironment and Drug Responses in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is notoriously deadly, in part because its dense tumor microenvironment (the mix of stromal fibroblasts and immune cells) shields cancer cells from drug therapeutics.

In this recent paper, Bishehsari’s team, including his PhD candidate and the first author, Darbaz Adnan, together with the GRC research group, developed an organ-on-a-chip platform seeded with patient-derived organoids (three-dimensional mini tumors generated from clinical samples) along with human endothelial cells, pancreatic stellate cells, and immune cells. The chip is perfused to mimic physiological blood flow, enabling a realistic recreation of the tumor microenvironment. As reported in Advanced Science, this organ-on-a-chip model faithfully recapitulates the cancer stroma interactions observed in human PDAC tumors.

By combining organoids with a microfluidic system and real human stromal/immune cells, the team has created an ex vivo platform to study cancer stroma interactions and to screen therapies in a patient-specific context.

The authors note that targeting the desmoplastic stroma significantly enhanced chemo effects, and that the chip may model immunotherapy response.

Overall, this work demonstrates a powerful patient-derived PDAC model for precision medicine.

Darbaz Adnan, MBChB, MS, is a doctoral candidate conducting translational research with Faraz Bishehsari, MD, PhD. His thesis focuses on patient-derived organoids and organ-on-a-chip platforms that integrate tumor microenvironment components to model pancreatic cancer and evaluate therapeutic responses ex vivo. He has co-authored multiple peer-reviewed publications in gastrointestinal research and has received several conference awards.

Dr. Arthur Beyder presents Grand Rounds for the GRC

In February, the GRC had the honor of hosting Dr. Arthur Beyder, Associate Professor of Medicine and Physiology at the Mayo Clinic, Rochester, MN, as our Internal Medicine Grand Rounds speaker and our guest at the DDC research forum.

Dr. Beyder presentation, titled The Gut as a Living Machine: How Mechanical Forces Shape GI Function and Disease, described how mechanical forces in the gastrointestinal tract influence normal motility, sensation and recognize clinical situations where these forces become abnormal. It illustrated how altered mechanotransduction contributes to common processes, like aging, and GI disorders such as functional dyspepsia, IBS, obstructive states, emphasizing mechanisms with translational relevance, and assessed opportunities to integrate mechanobiology into clinical decision-making, including diagnostic strategies for motility and sensation disorders and emerging therapeutic approaches that target mechanical signaling pathways.

Dr. Beyder runs an NIH-funded research program the aim of which is to determine the mechanisms of “gut feeling,” and, in particular, how these mechanisms can be used to understand and treat gastrointestinal motility disorders. His specific expertise is in the areas of mechanical and electrical aspects of the digestive system function. His work has focused on the cellular and molecular aspects of ion channel physiology and biophysics in the gut and how forces are sensed and transduced by these ion channels.

The Beyder group discovered gut touch, which is an intrinsic tactile sense in the gut that allows it to, like fingertips, determine the physical aspects of luminal contents to regulate motility and secretion. This work is transforming our knowledge of how the gut handles physical particulates and has important translational implications for Disorders of Gut Brain Interaction (DGBI).

We are happy to welcome Erin Wells as the Division Manager for GRC. Erin has been with the institution since 2016, serving in multiple roles within the Dean’s Administration and Faculty Affairs Office prior to joining Internal Medicine in 2024. She earned her bachelor’s degree from Texas A&M University and is completing her MBA at Texas Woman’s University this May. Erin enjoys spending time outside of work with her husband and their two cats, as well as reading, watching movies, and playing games.

Issue 4 – January 2026

New NIH R01 Secured to Investigate the Microbiome in Organ Injury

The newest initiative from the Gastroenterology Research Center focuses on understanding how the gut microbiome responds to environmental changes, such as chronic alcohol use, that affect the host responses and disease outcome. Environmental exposures including alcohol consumption are known to cause multiorgan damage, and growing evidence, including work from our own group, demonstrates that shifts in the gut microbiota play a major role in promoting this process by disrupting intestinal barrier and triggering local and systemic inflammation. Therefore, investigating organ injury-associated microbiome changes will provide critical insights into the mechanisms underlying organ damage and facilitate the development of microbiome-targeted therapeutic interventions.

With support from a newly awarded grant from the National Institute on Alcohol Abuse and Alcoholism, we are launching a project designed to address this critical knowledge gap. Our goal is to integrate multi-omics data, including metagenomics, transcriptomics, and metabolomics, to identify specific gut microbiome signatures (known as enterotypes) associated with organ damage in the setting of alcohol exposure. We will develop a comprehensive platform to integrate gut microbiota composition, microbial metabolites, host molecular pathways, and clinical phenotypic data into a unified, accessible online resource.

This tool will enable us to map the microbial signatures responsible for pathological responses to alcohol exposure and predict clinical outcomes of organ damage. This collaborative effort leverages our large repository of microbiome data, data science technologies and the population-based resources. UTHealth provides a real-world clinical setting to validate and test an interactive platform for enterotype identification and disease-outcome prediction. These combined efforts will enhance the module’s accuracy and usability, making it readily accessible to researchers across institutions and fostering collaborative research throughout the research community.

Paper Highlight of the Month!

Depletion of Fibrinogen Suppresses Growth of Primary Tumors and Metastasis of Pancreatic Ductal Adenocarcinoma (external link)

Pancreatic adenocarcinoma (PDAC) is a highly metastatic and aggressive cancer often characterized by elevated fibrinogen levels, both circulating and within the tumor microenvironment. The authors aimed to target fibrinogen to limit the cancer spread and progression. Using patient-derived pancreatic cancer models, the research attempted to target fibrinogen by using state-of-the-art, cutting-edge treatment approaches, such as antisense oligonucleotides and lipid nanoparticles containing small interfering RNAs. Reducing fibrinogen slowed tumor cell growth and decreased the growth of primary tumors in living models. The reduction also altered protein expression and led to fibrosis surrounding the tumor, favoring the presence of purely stromal forming cells. These cancer-associated fibroblasts restrain tumor growth and spread, when they normally promote tumor growth. Overall, this work shows that targeting fibrinogen actively shapes the primary tumor environment in ways that affect growth and early metastatic development. These findings point to a promising new direction for treatment by combining fibrinogen targeting strategies with standard chemotherapy to help limit the spread of pancreatic cancer.

Director of the Digestive Disease service line at Rush

On December 2025, the Gastroenterology Research Center (GRC) at UT McGovern Medical School hosted Dr. Irving Waxman, director of Digestive Diseases and Nutrition at Rush University Medical Center, as the invited Internal Medicine Grand Rounds speaker. Dr. Waxman delivered a presentation titled “Pancreatic Cystic Lesions: Diagnostic and Therapeutic Dilemma,” providing a comprehensive overview of the prevalence, morphology, and clinical relevance of pancreatic cystic lesions. His talk highlighted the rising detection of cysts with modern high-resolution imaging and reviewed distinguishing features between serous, mucinous, and premalignant lesions, with emphasis on risk indicators such as mural nodules and ductal involvement. Dr. Waxman also discussed current diagnostic strategies, including CT/MRI accuracy, EUS interpretation, cyst fluid CEA analysis, and advanced modalities such as EUS-guided FNA, micro-biopsy, and needle-based confocal laser endomicroscopy (nCLE). He reviewed evidence comparing these approaches and explained how newer technologies enhance diagnostic precision compared to cytology alone. Additionally, he summarized key guideline frameworks, including the AGA recommendations and updated Kyoto guidelines, outlining the ongoing challenge of balancing early cancer detection with the morbidity of pancreatic surgery. His lecture provided internal medicine faculty, trainees, and clinicians with an up-to-date, evidence-based framework for evaluating and managing pancreatic lesions.

Dr. Faraz Bishehsari spoke at the Dan L Duncan Comprehensive Cancer Center (DLDCCC) on December 16, 2025, as part of their Distinguished Lecture Series. The DLDCCC, housed within Baylor College of Medicine, is a National Cancer Institute, designated Comprehensive Cancer Center, recognized for its scientific excellence, cutting-edge cancer research, and commitment to reducing cancer burden through clinical care, education, and community outreach. It brings together extensive research programs, advanced clinical services, and multidisciplinary expertise under one institution, making it one of only three NCI-designated comprehensive cancer centers in Texas. During his lecture, Dr. Bishehsari discussed the role of circadian disruption in gastrointestinal cancers, focusing on how environmental and behavioral cues, such as light exposure and meal timing, shape colorectal cancer risk. He also highlighted emerging opportunities to leverage circadian biology in pancreatic cancer, emphasizing how time-based therapeutic approaches may strengthen both prevention and treatment strategies. Together, his insights underscored the growing importance of integrating chronobiology into cancer research and clinical care.

Paper Highlight of the Month!

Targeting Mutual Dependence of Phosphatidylinositol-3-Kinase α/δ and Small Ubiquitin-Like Modifier Signaling in Pancreatic Cancer (external link)
This 2025 Gastroenterology study by Hazal Köse et al. investigates why pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers, is so resistant to treatment and explores a new combination therapy approach. The authors focus on two key cellular pathways: PI3K signaling, which promotes cell growth and survival, and SUMOylation, a protein-modification process that helps cancer cells adapt to stress. Previous attempts to inhibit the PI3K pathway alone have largely failed because cancer cells rapidly activate alternative survival mechanisms. This study shows that PI3K activity and SUMOylation are mutually dependent in pancreatic cancer cells. When PI3K is inhibited, SUMOylation increases to compensate, allowing the tumor cells to survive. Similarly, blocking SUMOylation alone is insufficient because PI3K signaling remains active. The key finding is that simultaneous inhibition of both PI3K and SUMO pathways leads to a strong anti-tumor effect. Combined treatment reduces cancer cell survival, suppresses tumor growth in preclinical models, and improves anti-tumor immune responses by making the tumor microenvironment less immunosuppressive. Overall, this study identifies a critical vulnerability in pancreatic cancer biology and suggests that dual targeting of PI3K and SUMOylation could overcome therapy resistance. While these results are preclinical, they provide a strong rationale for future clinical trials using combination strategies in PDAC.

The GRC extends our warmest wishes for a joyful holiday season and a healthy, successful New Year. We are grateful for the dedication, collaboration, and support that made this year meaningful and productive. Thank you for being part of our community. We look forward to continued growth, discovery, and partnership in the year ahead.

Inside GRC: Advancing Precision Medicine for Pancreatic Cancer:
Bishehsari’s study on pancreatic cancer at GRC is seeking to develop new ways to personalize treatment for pancreatic ductal adenocarcinoma.

This project aims to develop a precision medicine platform for circadian-based therapeutics in pancreatic cancer. The work is supported by a renewal of Bishehsari’s NIH Transformative R01 and an R03. Bishehsari is the first gastroenterologist-scientist honored with the NIH Director’s Transformative Research Award, one of the most prestigious and selective grants offered by the NIH. According to the NIH, this mechanism “supports exceptionally creative scientists proposing bold and unconventional research with the potential to revolutionize biomedical science”.

Pancreatic ductal adenocarcinoma is an aggressive cancer that is challenging to treat. Our circadian clock acts like an internal timer that regulates sleep, energy, and digestion. In cancer, this clock can be rewired to support tumor growth and energy demands. This project seeks to decode tumor-specific circadian signatures to uncover novel therapeutic options.

Combining wet lab techniques that interrogate clock function in human pancreas with systems biology approaches, Bishehsari’s team aims to determine whether tumor rhythm alterations affect patient outcomes and how aligning treatments with a patient’s tumor rhythm and identifying new targets for chronotherapy could improve treatment efficacy for pancreatic cancer and potentially other cancers.

Summer Students
During the previous summer, our laboratory had the privilege of hosting three students through the Visiting Students Program. Priya Verma and Kate Chin, both second-year
undergraduates at Rice University, joined us to gain early exposure to research in gastroenterology. In addition, Sejiro Tokutsu, a fourth-year medical student from Tokushima University School of Medicine in Osaka, Japan, participated in the program to deepen his understanding of translational research. Their time in the lab provided valuable opportunities for academic growth and cross-cultural exchange, while contributing meaningfully to ongoing projects.

Kate and Priya, both on the pre-medical track, are investigating the chronotherapy treatment efficacy in pancreatic ductal adenocarcinoma. This research not only deepens their understanding of cancer and circadian biology but equips them with critical translational research experience, preparing them for the rigors of medical school and their future roles as physicians.

Paper Highlight of the Month!
Kate is reading: Comparative Evaluation of Droplet- and Picowell-Based Single-Cell RNA Sequencing for Human Mucosal Biopsies “This study investigating the involvement of Josephin domaincontaining protein 2 (JOSD2) in the progression of acute pancreatitis found elevated JOSD2 expression levels in the pancreatic tissue of mice with cerulein-induced Acute Pancreatitis. (AP). Subsequent experimentation found reduced edema and inflammatory markers in JOSD2 knockout mice in cerulein and Larginine
induced AP. More specifically, researchers found that pancreatic acinar cell specific JOSD2, rather than myeloid JOSD2, mediates cerulein-induced AP through removing K63-linked polyubiquitin chains from Proliferating Cell Nuclear Antigen (PCNA) at the K164 site.” Read it here (external link)

Priya is reading: Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoid “This paper describes the synthesis and testing of 3D pancreatic organoid culture media with differing levels of stiffness. PDAC tumors are highly fibrotic in vivo, and researchers have theorized
that this contributes to their strong resistance to most conventional chemotherapy. This paper showed stronger gemcitabine chemoresistance when PDAC cells were cultured in stiffer culture matrix, opening up another possible reason for PDAC’s strong chemoresistance. These findings align with ongoing work in Bishehsari’s lab, which is investigating how stiffness influences primary cancer cells and the tumor microenvironment. You can read about the paper more at: Read it here (external link)

In November, Luca Santovito, Samana Fatima, Jessica Wang, and Sommer Durrani represented the Gastroenterology Research Center (GRC) at the McGovern Medical School Research Fair, where they showcased our work to medical students interested in gastroenterology research. Our lab offers opportunities in both bench work and clinical research through chart reviews. Students can gain exposure to translational science and hands-on experience working with cells and organoids. We are currently welcoming new students who wish to contribute to our research initiatives. Interested individuals are encouraged to contact us for further information.

On the Left: The GRC hosted a dinner to welcome new team members Sommer, Connor, and Wankun. While we celebrated these exciting additions, we also bid a heartfelt farewell to Donyea Moore as she embarks on her journey to medical school.
 
 
 

The Gastroenterology Research Center (GRC) is an integrative program committed to advancing education, research, and clinical care in alignment with UTHealth Houston’s mission. The center conducts cutting-edge research on the digestive system, focusing on preventive strategies, disease modification, treatment innovations, and emerging technologies. Our team investigates how the digestive tract interacts with lifestyle factors in contributing to organ damage, including age-related conditions and cancer. Through a multidisciplinary approach, we aim to uncover disease mechanisms that can be directly translated into patient care from risk assessment and prevention to the development of novel therapeutics.

Director of the Gastroenterology Research Center (GRC), a new multidisciplinary gastroenterology research center at McGovern Medical School. The GRC integrates translational research with patient care, focusing on the role of the digestive tract in health and diseases.

Director’s Message: Celebrating Our Team and Mission
As founder and director of the Gastroenterology Research Center (GRC) at UT McGovern Medical School, I am proud of the remarkable work led by our multidisciplinary team. Our collaborative research across the digestive tract focuses on prevention, disease modification, therapeutic innovation, and advanced technologies. We employ in vivo and ex vivo modeling, microbiology, chronobiology, immunology, and data science.

By integrating cutting-edge patient-based platforms such as organoids, organ-chips, and biosensors, we aim to accelerate translational discovery. Our team is particularly interested in how circadian rhythms, gastrointestinal microorganisms, and the tissue microenvironment influence organ aging signals, carcinogenesis, and treatment outcomes. We seek to identify targetable mechanisms and biomarkers to inform future therapies.

I am deeply grateful to UT McGovern Medical School for its steadfast support and to the NIH for funding our independent scientific inquiry. Looking ahead, we are eager to engage with the broader community and philanthropic partners to build a future where science and compassion come together to transform lives. It is an honor to lead such an extraordinary group.

Warm regards,
Faraz Bishehsari, MD, PhD
Director, GRC
UT McGovern Medical School

Paper Highlight of the Month!

Circadian Rhythms in Gastroenterology: The Biological Clock’s Impact on Gut Health (external link)
The paper titled “Circadian Rhythms in Gastroenterology: The Biological Clock’s Impact on Gut Health” is a review article published in the journal Gastroenterology In this paper, we discuss how circadian rhythm, our internal biological clocks, regulate gastrointestinal (GI) functions and how disruptions to these rhythms can contribute to a range of GI disorders. It also discusses potential circadian-based therapeutic strategies, such as optimizing medication timing and lifestyle interventions to restore circadian alignment.

We extend our deepest gratitude to Senaida Perez, our interim administrator, alongside Norma Amaya-Hernandez, and Joseph Handy, whose early support of the GRC was invaluable in making the center what it is today.