Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
APOE was marker for defining a long term survivor and short term survivor for ovarian cancer patients; the markers were in the stroma
there is spatial communication between tumor and underlying stroma
it is imperative to understand how your multiomics equipment images a tumor area before it laser captures and send to the MS system; can lose a lot of tissue and information based on differences in resolution
many of these multiomics systems are validated for the clinic in EU not US
multiomics spatial analysis allows you to image protein, metabolite, mRNA expression in the 3 dimensional environment of the tumor (tumor cells and stroma)
they are making a human tumor atlas
they say a patient who had tumor went home during COVID and took vaccine but got ill with vaccine; but came back to check tumor and tumor had greatly regressed because prevaccine the tumor was immunologically cold and post COVID vaccine any left over tumor showed great infiltration of immune cells
BD Bioscience multiomics platform is modular and can add more omics levels in the platorm
for example someone wanted to look at T cells
people have added CRISPR screens on the omics platform
most people are using single cell spatial omics
they have a FACS on their platform too so you can look at single cell spatial omics and sort different cellular populations
very comparative to 10X Genomics platform
their proteomics is another layer you can add on their platform however with proteomics you can high background notice with spatial proteomics or a limited panel of biomarkers
Their OMICS Protein One panels are optimized for biology and tumor type.
get high quality multiomics data and proteomics data but in a 3D spatial format
developed Cellismo Data Visualization software tool
4:55-5:10
Harsha Gowda, PhD, Senior Principal Scientist, Director, Research & Lab Operations, Signios Bio
Signios Biosciences (Signios Bio) is the US-based arm of MedGenome, a global leader in genetic testing services, genomics research, and drug discovery solutions.
Signios Bio is a multiomics and bioinformatics company dedicated to revealing the intricate signals within biological data. We leverage the power of multiomics—integrating data from genomics, transcriptomics, proteomics, epigenomics, metabolomics, and microbiomics—to gain a comprehensive understanding of disease biology. Our AI-powered bioinformatics platform allows us to efficiently analyze these complex datasets, uncovering hidden patterns and accelerating the development of new therapies and diagnostics.
Through the integration of cutting-edge multiomics technologies, advanced bioinformatics, and the expertise of world-class scientists, we enable researchers and clinicians with comprehensive, end-to-end solutions to improve drug discovery and development and advance precision medicine.
As part of MedGenome, we have access to real-world evidence (RWE) from global research networks across the US, Europe, Asia, Africa, Middle East, and Latin America. This access enables us to work with our partners to uncover insights that can lead to new biomarkers and drug targets, ensuring that precision medicine is inclusive and effective for all.
The Payload Revolution: Redefining the Future of Antibody-Drug Conjugates (ADCs)
Curator: Dr. Sudipta Saha, Ph. D.
Antibody-Drug Conjugates (ADCs) are at the forefront of targeted cancer therapy. While much attention has focused on antibody engineering and linker technology, the real breakthrough may lie in the payload—the cytotoxic compound delivered to tumor cells.
Historically, ADC payloads have relied on microtubule inhibitors like MMAE and MMAF, and topoisomerase I inhibitors such as SN-38 and Exatecan. These payloads are potent but limited in diversity, making differentiation difficult in a crowded therapeutic landscape.
The next wave of innovation introduces unconventional payloads with novel mechanisms:
ISACs (Immune-Stimulating ADCs) activate the immune system locally.
Protein degraders eliminate cancer-critical proteins without inhibiting them directly.
Urease-based and membrane-disrupting agents affect the tumor microenvironment.
RNA polymerase inhibitors and peptide-based payloads offer precision with reduced systemic toxicity.
This shift also places new demands on linker design. Linkers must now accommodate payloads with diverse chemical properties and release them selectively at the tumor site. A payload–linker mismatch could compromise both safety and efficacy.
Ultimately, the focus is shifting toward payloads not just as cytotoxins, but as precision-guided interventions. This evolution could redefine how ADCs are developed and positioned in treatment regimens, enabling breakthroughs in resistant and heterogeneous cancers. The ADC revolution is payload-powered—and the future belongs to those who can innovate at the molecular level.
Protein Switches: The Programmable Future of Bio-therapeutics
Curator: Dr. Sudipta Saha, Ph. D.
A PNAS paper entitled “A protein therapeutic modality founded on molecular regulation” presents a pioneering approach to creating protein switches—engineered enzymes that activate only in specific molecular environments. This design introduces a new class of context-dependent therapeutics for precision medicine.
Using domain-insertion techniques, researchers inserted ligand-binding domains into scaffold proteins like β-lactamase. These proteins remain inactive until encountering a specific small molecule, which triggers a conformational change and restores enzymatic activity. This offers precise spatiotemporal control—ideal for minimizing off-target effects.
One key innovation is the systematic insertional mutagenesis that identifies functional switch sites across the protein scaffold. This enables the construction of vast protein libraries, increasing the likelihood of finding optimal switch configurations. Furthermore, the approach is modular—different binding domains and enzymes can be combined to create switches tailored to specific clinical contexts.
These smart proteins can be programmed to respond to cancer biomarkers, metabolite levels, or disease-specific molecular cues. By activating only under disease conditions, they provide a blueprint for next-generation bio-therapeutics—potent, selective, and safer.
The method also opens avenues for drug delivery systems, diagnostics, and biosensors, where conditional activation is critical. Overall, this work represents a conceptual leap in synthetic biology and bioengineering, with implications spanning oncology, infectious disease, and regenerative medicine.
Immuno-Timebombs: The Hidden Drivers of Age-Related Illness
Curator: Dr. Sudipta Saha, Ph. D.
There are two converging biological processes that drive most age-related diseases: immunosenescence and inflammaging. Together, they explain how a deteriorating immune system and chronic low-grade inflammation contribute to neurodegenerative diseases, cancer, cardiovascular disorders, and frailty.
Immunosenescence refers to the waning competence of both innate and adaptive immune systems. With age, T and B cells become less effective, and macrophage function declines. This makes older individuals more susceptible to infections and less efficient at clearing dysfunctional cells.
Inflammaging, on the other hand, is the persistent presence of inflammation without infection. Factors like gut microbiome alterations, senescent cell accumulation, and epigenetic drift contribute to this condition. Over time, this “silent fire” damages tissues and lays the groundwork for disease.
These drivers don’t just correlate with disease—they often precede it. This positions inflammaging and immunosenescence as targets for prevention, not just treatment. Interventions like exercise, caloric modulation, and anti-inflammatory diets may attenuate their effects. Emerging therapies such as senolytics and immune rejuvenation approaches (e.g., thymic regeneration) are showing promise.
This article also calls for a paradigm shift in medical science—from reactive disease management to proactive longevity interventions. As we unravel the biological clocks of aging, strategies targeting immune recalibration may delay or prevent multiple diseases simultaneously.
The future of healthy aging may well depend on how early we can intervene in this immuno-inflammatory loop—before pathology sets in.
A multicenter retrospective cohort study published in The Lancet has evaluated the effectiveness of GLP-1 receptor agonists (GLP-1 RAs), including semaglutide and tirzepatide, versus bariatric surgery in managing type 2 diabetes and obesity. The study was conducted using data from real-world clinical settings involving adults with type 2 diabetes and a body mass index (BMI) over 30.
Patients treated with GLP-1 RAs were found to have significant improvements in glycemic control and weight loss; however, bariatric surgery led to more pronounced and sustained reductions in HbA1c and body weight over a 2-year follow-up. Cardio-metabolic benefits, including blood pressure and lipid profile improvements, were also more prominent in the surgery group.
Despite this, GLP-1 RAs were associated with a lower incidence of early complications and shorter recovery times. Adverse gastrointestinal events were commonly reported in both groups, though surgical complications were more severe but less frequent.
This study suggested that while bariatric surgery remains the most effective intervention for sustained weight and glycemic outcomes, GLP-1 RAs offer a safer, non-invasive alternative with substantial benefit, particularly for patients ineligible or unwilling to undergo surgery. The potential for GLP-1 RA therapy to delay or reduce the need for surgical intervention was also discussed.
These findings have emphasized the importance of personalized treatment strategies based on patient comorbidities, preferences, and risk profiles.
Unlocking the Secrets of Longevity: A 117-Year-Old Woman’s Genes Defied Aging
Curator: Dr. Sudipta Saha, Ph.D.
A recent study led by the University of Barcelona has shed light on the genetic factors contributing to exceptional human longevity. The research focused on Maria Branyas Morera, who was recognized as the world’s oldest living person until her passing at age 117 in August 2024. The findings revealed that her unique genetic makeup allowed her cells to function as if they were 17 years younger, and her gut microbiota resembled that of an infant.
Branyas Morera attributed her remarkable lifespan to “luck and good genetics.” Beyond her genetic advantages, she maintained a healthy lifestyle characterized by a Mediterranean diet, regular physical activity, and strong family bonds. These factors likely contributed to her prolonged cognitive clarity and minimal health issues, primarily limited to joint pain and hearing loss.
This study adds to a growing body of research exploring the genetic foundations of longevity. For instance, the Okinawa Centenarian Study has examined over 600 centenarians from Okinawa, Japan, uncovering genetic markers associated with extended lifespan and reduced incidence of age-related diseases.
Similarly, the New England Centenarian Study has identified specific genetic variations linked to longevity, providing insights into the biological mechanisms that allow some individuals to live significantly longer than average.
Researchers hope that understanding these genetic factors can inform the development of treatments for age-related diseases, challenging the notion that aging and illness are inextricably linked. By studying individuals like Branyas Morera, scientists aim to uncover strategies to promote healthier aging across the broader population.
However, it’s important to note that while genetics play a crucial role in exceptional longevity, lifestyle factors such as diet, exercise, and social connections also significantly impact overall health and lifespan. The interplay between genetic predisposition and environmental influences continues to be a critical area of research in understanding human aging.
Nearly half of the global population—and 80 percent of patients in therapeutic areas such as immunology—are women. Yet, treatments are frequently developed without tailored insights for female patients, often ignoring critical biological differences such as hormonal impacts, genetic factors, and cellular sex. Historically, women’s health has been narrowly defined through the lens of reproductive organs, while for non-reproductive conditions, women were treated as “small men.” This lack of focus on sex-specific biology has contributed to significant gaps in healthcare.
A recent analysis found that women spend 25 percent more of their lives in poor health compared with men due to the absence of sex-based treatments. Addressing this disparity could not only improve women’s quality of life but also unlock over $1 trillion in annual global GDP by 2040.
Four key factors contribute to the women’s health gap: limited understanding of sex-based biological differences, healthcare systems designed around male physiology, incomplete data that underestimates women’s disease burden, and chronic underfunding of female-focused research. For instance, despite women representing 78 percent of U.S. rheumatoid arthritis patients, only 7 percent of related NIH funding in 2019 targeted female-specific studies.
However, change is happening. Companies have demonstrated how targeted R&D can drive better outcomes for women. These therapies achieved expanded FDA approvals after clinical trials revealed their unique benefits for female patients. Similarly, addressing sex-based treatment gaps in asthma, atrial fibrillation, and tuberculosis could prevent millions of disability-adjusted life years.
By closing the women’s health gap, biopharma companies can drive innovation, improve therapeutic outcomes, and build high-growth markets while addressing long-standing inequities. This untapped opportunity holds the potential to transform global health outcomes for women and create a more equitable future.
Chicoric Acid: A Natural Boost for Glucose Metabolism via AMPK Activation
Reporter: Dr. Sudipta Saha, Ph.D.
The study published in Journal of Functional Foods explores the molecular mechanisms underlying chicoric acid’s (CA) role in glucose metabolism. Chicoric acid, a natural polyphenolic compound found in plants like chicory and basil, has garnered attention for its anti-inflammatory and antidiabetic properties. The researchers investigated its potential to regulate glucose uptake and insulin sensitivity, focusing on the AMP-activated protein kinase (AMPK) pathway.
The experiments demonstrated that chicoric acid significantly enhances glucose uptake in insulin-sensitive and insulin-resistant cells. This effect was primarily mediated through the activation of AMPKα, a key metabolic regulator that responds to energy stress. The phosphorylation of AMPKα triggered downstream signaling cascades, including the activation of Akt, a protein crucial for glucose transporter type 4 (GLUT4) translocation to the cell membrane, thereby facilitating glucose uptake.
Interestingly, the study also noted that inhibiting AMPK activity reduced CA-induced Akt phosphorylation, confirming that AMPK activation is essential for chicoric acid’s metabolic effects. Furthermore, CA showed potential in improving insulin sensitivity, which is impaired in type 2 diabetes, by mitigating cellular oxidative stress and inflammation.
The findings suggest that chicoric acid could serve as a promising therapeutic candidate for managing diabetes and metabolic disorders. By targeting the AMPKα-Akt signaling axis, CA offers a dual benefit of improving glucose metabolism and reducing insulin resistance, highlighting its potential as a natural alternative for metabolic health interventions.
Xenotransplantation: Pioneering a New Era of Organ Availability
Reporter: Dr. Sudipta Saha, Ph.D.
The 2024 World Medical Innovation Forum (WMIF) spotlighted xenotransplantation as a transformative solution to the organ shortage crisis. By leveraging genetically modified pig organs, this emerging field offers a new source of transplants, expanding life-saving care options.
Key breakthroughs in 2024 have brought new hope for patients, but significant hurdles remain, including immunological rejection. Ongoing research focuses on developing immunosuppressive strategies and enhancing organ compatibility.
Collaboration between scientists, clinicians, and regulatory bodies is essential for xenotransplantation’s future. Experts predict wider clinical availability within the next decade, potentially reshaping organ replacement.
This revolutionary step in organ transplantation holds promise for patients and could redefine the future of transplant care globally. Here’s a comprehensive report covering the research contributions of the panelists from the Xenotransplantation: Game Changing Organ Replacement discussion:
1. Jason Gerberry
Specialty Pharma and SMid-Cap Biotech Analyst, BofA Global Research
Gerberry is a prominent financial analyst with deep expertise in specialty pharmaceuticals and small-to-mid-cap biotechnology firms. His research focuses on investment trends, market dynamics, and the financial viability of innovative medical solutions such as xenotransplantation. At WMIF 2024, he provided insights on how breakthroughs in the field could impact the biotech sector, including the potential for significant investments driven by advancements in gene editing and organ transplantation technologies. Gerberry’s analysis offers critical perspectives on the commercial and economic landscape surrounding xenotransplantation.
2. Joren Madsen, MD, PhD
Director, MGH Transplant Center
Paul S. Russell/Warner-Lambert Professor of Surgery, Harvard Medical School Dr. Madsen is a leader in transplant surgery and immunology. His research focuses on allograft rejection and immunosuppressive strategies to enhance transplant tolerance. He has been pivotal in advancing clinical transplant practices at Massachusetts General Hospital (MGH) and has made significant contributions to xenotransplantation research by exploring how genetically engineered pig organs could help mitigate immune rejection in human recipients. Madsen’s work is key to translating laboratory findings into clinical applications.
3. Tatsuo Kawai, MD, PhD
Director of the Legorreta Center for Clinical Transplantation Tolerance
A. Benedict Cosimi Chair in Transplant Surgery, MGH
Dr. Kawai specializes in immune tolerance and organ transplantation. His research emphasizes reducing or eliminating the need for lifelong immunosuppressive drugs in transplant patients. He has led groundbreaking clinical trials on tolerance induction, paving the way for the potential acceptance of xenotransplanted organs without rejection. His research is also closely tied to immune tolerance mechanisms and how xenotransplantation can be made safer for human use.
4. Richard Pierson III, MD
Scientific Director, Center for Transplantation Sciences, MGH
Professor of Surgery, Harvard Medical School
Dr. Pierson is renowned for his work in transplantation immunology, focusing on xenotransplantation. His research addresses the fundamental problem of immune rejection of animal organs in human bodies, particularly tackling hyperacute rejection and graft survival. Dr. Pierson has been instrumental in developing strategies to overcome these barriers by modifying pig genetics and using innovative immunosuppressive therapies, which have brought the field closer to clinical application.
5. Leonardo Riella, MD, PhD
Medical Director of Kidney Transplantation, MGH
Harold and Ellen Danser Endowed Chair in Transplantation, Harvard Medical School
Dr. Riella’s research focuses on kidney transplantation and immunosuppressive therapies aimed at improving long-term graft survival. He has been a significant contributor to the field of xenotransplantation, working on improving immune tolerance and understanding how kidneys from genetically modified pigs can function in human bodies without eliciting strong immune responses. His clinical and translational research is critical for the future of xenotransplantation, particularly in renal applications.
Conclusion
These panelists represent leading voices in xenotransplantation, combining their expertise in surgery, immunology, and biotechnology to address the complex challenges of organ transplantation. Their collaborative efforts at MGH and Harvard Medical School are critical in advancing the science of xenotransplantation, bringing it closer to a clinically viable solution for the global organ shortage crisis.
Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use
In this curation we wish to present two breaking through goals:
Goal 1:
Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer
Goal 2:
Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.
According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.
These eight subcellular pathologies can’t be measured at present time.
In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.
Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases
Glycation
Oxidative Stress
Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
Membrane instability
Inflammation in the gut [mucin layer and tight junctions]
Epigenetics/Methylation
Autophagy [AMPKbeta1 improvement in health span]
Diseases that are not Diseases: no drugs for them, only diet modification will help
Image source
Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease
These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:
Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL
In the Bioelecronics domain we are inspired by the work of the following three research sources:
Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia
THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC
PENDING
THE VOICE of Stephen J. Williams, PhD
Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes
25% of US children have fatty liver
Type II diabetes can be manifested from fatty live with 151 million people worldwide affected moving up to 568 million in 7 years
A common myth is diabetes due to overweight condition driving the metabolic disease
There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
Thirty percent of ‘obese’ people just have high subcutaneous fat. the visceral fat is more problematic
there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects. Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
At any BMI some patients are insulin sensitive while some resistant
Visceral fat accumulation may be more due to chronic stress condition
Fructose can decrease liver mitochondrial function
A methionine and choline deficient diet can lead to rapid NASH development