The Rising Star Power Talks at ENDO showcase early-career and in-training members who present concise, high-impact summaries of their research. At ENDO 2026, 15 emerging investigators competed in a blitz-style communication format judged by both academic and industry representatives. Konstantinos Stefanakis, MD, PhD (candidate), a cardiology fellow and postdoctoral research fellow at Harvard Medical School and Beth Israel Medical Center in Boston, was selected as the Audience’s Choice winner. The session highlights the Endocrine Society’s role in providing visibility and community for developing investigators.
Stefanakis presented work from the Mantzoros Laboratory that uses blood-based omics, with a focus on circulating proteomics, to characterize metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). The study analyzed serum and plasma proteins from patients whose liver disease stage was defined by biopsy. The team asked whether circulating proteins change with progressive disease stages and whether those proteomic alterations correspond to key biopsy features such as inflammatory activity and fibrosis.
The rationale is clinical: MASH is part of a broader metabolic disease spectrum often coexisting with obesity, insulin resistance, type 2 diabetes, dyslipidemia, and elevated cardiovascular risk. MASH can progress to advanced fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Although treatments for at-risk MASH (MASH with moderate to advanced fibrosis) are now available, identifying patients who would benefit remains challenging. Liver biopsy is definitive but invasive and impractical for broad screening. Current non-invasive tests (NITs) are useful for fibrosis risk stratification but may not reveal the active pathogenic biology driving disease in individual patients.
Stefanakis and colleagues propose that proteomics could add a biological layer to existing NITs, potentially improving patient selection for referral, treatment, clinical trials, and monitoring by reflecting inflammation, metabolic stress, tissue remodeling, and fibrosis directly in circulating proteins.
The project was inspired and guided by Stefanakis’s mentor, Dr. Christos Mantzoros, and by the translational research environment of the Mantzoros Laboratory. Stefanakis described learning from his mentor the importance of identifying unmet clinical needs and addressing them with rigorous translational approaches. The lab’s broader mission includes studying obesity, diabetes, metabolic disease, and cardio-renal-liver-metabolic complications with the objective of improving patient care.
Stefanakis emphasized the clinical gap he aimed to address: in routine practice, it remains difficult to distinguish mild from active progressive disease without relying on surrogate tests or liver biopsy. The proteomics project seeks to provide a more direct window into disease pathophysiology across stages, with practical goals such as reducing unnecessary invasive procedures, recognizing progressive disease earlier, and better selecting patients for new therapies.
Presenting this work at ENDO felt particularly appropriate to Stefanakis because MASLD and MASH intersect with endocrine and metabolic conditions that are commonly managed by endocrinologists. He described the experience as humbling and motivating, noting that the collaborative nature of the project reflected contributions from the Mantzoros Laboratory.
Stefanakis valued the post-presentation discussion, which was scientifically engaging and yielded suggestions for next steps. Attendees raised considerations such as integrating transcriptomics and additional biological layers to strengthen the findings and exploring how proteomic tests might be applied in clinical pathways for risk stratification, referral, treatment selection, and monitoring.
Stefanakis attributes substantial career support and development to the Endocrine Society. He received the Summer Research Fellowship (REGMS) in 2020, which he described as critical early support that provided encouragement, visibility, mentorship, and momentum. Since then, he has received the Outstanding Abstract Award at ENDO from 2022 through 2026 and has published work in Endocrine Society journals. He noted the Mantzoros Laboratory’s recognition within the Society, including awards and fellowship recipients among mentor and trainees, which he finds meaningful for continuity across mentorship generations.
Stefanakis said that ENDO has provided a scientific home where his work at the intersection of endocrinology, obesity, diabetes, liver disease, and cardiometabolic risk naturally fits and where collaborations and community have supported his growth.
Looking ahead, Stefanakis outlined a deliberate path from discovery to clinical application. Discovery proteomics can screen thousands of proteins, but the aim is to identify robust biological signatures that can be validated, simplified, and developed into clinically useful non-invasive tests. He stressed that the objective is not indefinite measurement but rather to distill reliable biomarkers that translate to the clinic.
Planned next steps include validation of candidate proteomic signatures, translation into practical assays, and integration with other data layers—clinical variables, imaging, metabolomics, hormones, genetics, and transcriptomics—to create more powerful NITs. Such multi-omics approaches could improve identification of patients with active MASH, prediction of progression risk, and selection of those most likely to benefit from treatments.
Stefanakis framed these steps within a public health context: MASLD affects a large proportion of the global population and is tightly linked to obesity, type 2 diabetes, and cardiovascular disease. Better non-invasive tools could enable earlier detection of progressive disease, reduce unnecessary biopsies, optimize therapy allocation, and enable more rational longitudinal monitoring.
Through continuing validation and translational work, the research aims to move proteomic signatures from discovery-stage findings into tools that can meaningfully change clinical decision-making for patients with MASLD and MASH.