Roy lab

CSO Simmaron Research ; MIDD member, @RedefiningMECFS; CoFounder/Sci. Director of SIMMPHARM: Professor (adj) @UWM; Neurobio; ME/CFS; Drug design and development

[Roy lab @ProfAvikRoy]

Our team has discovered two promising small molecules, collectively named SIMMPYRAs, that target STAT3, a critical cellular signaling protein and a downstream effector of mTOR signaling.

Our studies have demonstrated that these molecules inhibit the production of key inflammatory mediators, including IL-6 and RANTES (CCL5), which have been implicated in ME/CFS pathogenesis. These findings provide an exciting opportunity to explore novel approaches to modulating inflammatory signaling in ME/CFS.

Beyond their potential relevance to ME/CFS, preclinical investigations have also demonstrated that SIMMPYRAs can inhibit the progression of triple-negative breast cancer, highlighting their broader therapeutic potential.

Our latest research findings on these novel small molecules have been published in the prestigious journal Cell Chemical Biology and are forthcoming in press.

At Simmaron Research, we believe that understanding disease mechanisms must go hand in hand with developing therapeutic interventions. This collaborative drug discovery initiative represents an important step toward bridging the gap between basic research and therapeutic development.

https://t.co/qtYJwr51EF

@CellPressNews @CellChemBiol @BreastCancerNow @TNBCFoundation @RedefiningMECFS @UWM

[Roy lab @ProfAvikRoy]

@TobiasPHD We have not yet established whether these effects translate into reduced circulating IL-6 and RANTES levels in individuals with ME/CFS. This will be an important component of our subsequent translational studies as we advance these compounds toward clinical development.

[Roy lab @ProfAvikRoy]

Our team has discovered two promising small molecules, collectively named SIMMPYRAs, that target STAT3, a critical cellular signaling protein and a downstream effector of mTOR signaling.

Our studies have demonstrated that these molecules inhibit the production of key inflammatory mediators, including IL-6 and RANTES (CCL5), which have been implicated in ME/CFS pathogenesis. These findings provide an exciting opportunity to explore novel approaches to modulating inflammatory signaling in ME/CFS.

Beyond their potential relevance to ME/CFS, preclinical investigations have also demonstrated that SIMMPYRAs can inhibit the progression of triple-negative breast cancer, highlighting their broader therapeutic potential.

Our latest research findings on these novel small molecules have been published in the prestigious journal Cell Chemical Biology and are forthcoming in press.

At Simmaron Research, we believe that understanding disease mechanisms must go hand in hand with developing therapeutic interventions. This collaborative drug discovery initiative represents an important step toward bridging the gap between basic research and therapeutic development.

https://t.co/qtYJwr51EF

@CellPressNews @CellChemBiol @BreastCancerNow @TNBCFoundation @RedefiningMECFS @UWM

[Roy lab @ProfAvikRoy]

@BetweenThieves7 Thank you for your support.

[Roy lab @ProfAvikRoy]

These compounds can be synthesized at the Milwaukee Institute for Drug Discovery (MIDD). However, before advancing them into human clinical trials, we must complete the necessary preclinical development and submit an Investigational New Drug (IND) application to the U.S. FDA to obtain authorization for human testing.

[Simmaron Research @RedefiningMECFS]

Take a scroll break and listen to the next step in our Rapamycin treatment trial for #MECFS and #LongCovid. Dr. Gunnar Gottschalk provides a look forward as we start gearing up for a double blind placebo trial. #GivingTuesday

[Roy lab @ProfAvikRoy]

The rationale for selecting mTOR (mechanistic target of rapamycin) as a central regulatory molecule to investigate in ME/CFS is that it sits at the intersection of several fundamental biological processes that are frequently disrupted in chronic diseases, including cellular metabolism, mitochondrial function, immune regulation, inflammation, protein synthesis, and autophagy.
Unlike molecules that regulate a single downstream pathway, mTOR acts as a master signaling hub that integrates information about nutrient availability, cellular energy status, growth factors, and environmental stress. Through these signals, it determines whether cells prioritize growth and metabolic activity or cellular maintenance, repair, and recycling.

[Roy lab @ProfAvikRoy]

Excited to announce that Simmaron Research has received a new NIH grant to advance our research into understanding the role of mTOR activation in the pathogenesis of ME/CFS.

This award represents an important milestone in our efforts to unravel the underlying molecular mechanisms of this complex and debilitating disease and identify potential new therapeutic targets.

We are grateful to everyone who has contributed to making this research possible and look forward to the discoveries ahead!

Explore the grant on NIH RePORTER:
https://t.co/Ncnel3hCBO

[AgelessRx @agelessrx_]

@RedefiningMECFS @ggottschalkPhD @ProfAvikRoy Appreciate Simmaron highlighting this work. There’s a real need for more rigorous research in ME/CFS, POTS, and Long COVID, and we’re proud to help build the evidence base around Rapamycin.

[Roy lab @ProfAvikRoy]

Rapamycin may tie these three converging threads together in ME/CFS. @RedefiningMECFS @UWM @SpringerNature @ggottschalkPhD

The link of our newest article
https://t.co/Bffs0TddKN

[Roy lab @ProfAvikRoy]

@VirusesImmunity @GrachStephanie @NatRevImmunol This is true and I respect your opinion on nurturing the practice for self-criticism for the sake of scientific integrity. I believe it makes scientists humble and receptive.

[Roy lab @ProfAvikRoy]

Rapamycin may tie these three converging threads together in ME/CFS. @RedefiningMECFS @UWM @SpringerNature @ggottschalkPhD

The link of our newest article
https://t.co/Bffs0TddKN

[Roy lab @ProfAvikRoy]

Our lab @RedefiningMECFS is a part of drug discovery consortium with MIDD @UWM. A collaborative research (Redox Biology; IF 11.9) identified a novel boronated prodrug that kills TNBC tumor cells by augmenting the production of reactive oxygen species.
https://t.co/9RaxuzT4xY

[Roy lab @ProfAvikRoy]

@BagarijitDr Congratulations

[Roy lab @ProfAvikRoy]

@SagarH62 Dean Jones

[Solve ME/CFS Initiative @PlzSolveCFS]

Watch! Dr. Avik Roy & Dr. Gunnar Gottschalk of @RedefiningMECFS share how six years of work on the molecular mechanisms of #MECFS has led to one of the only ongoing clinical trials specifically designed around a defined biological target.
https://t.co/axR1nyC1Ev
#MEAwarenessHour

[Roy lab @ProfAvikRoy]

@1DAVID92 @AhmedGT_ @AshuKharwa66211 @GarhManmohan @avnisharya123 @imD12kunal @Mushara78386844 The cut-off at higher end will make this stat interesting, which is maximum 15 balls.

[Roy lab @ProfAvikRoy]

Our team @RedefiningMECFS @ggottschalkPhD continues to perform ground-breaking research in decoding the role of ATG13 in chronic inflammation and now our new research (Toriola M https://t.co/WYpvXqg8Oq.) is now published in @SpringerNature’s Q1 immunology journal Inflammation Research.
https://t.co/LHUUCTKTOj


Background: CD40 is a key surface antigen expressed on macrophages and other myeloid cells, where it plays a central role in innate immunity by sustaining their inflammatory phenotype. In our earlier study (Immunologic Res 2025) , we demonstrated that the impaired autophagy can trigger sub-threshold infiltration of CD40-immunoreactive macrophages into the vasculature of skeletal muscle tissue. This infiltration contributes to chronic inflammatory changes affecting muscle-serving nerve fibers.

Findings: In our current work, we delineate the underlying mechanism. We demonstrate that the genetic depletion of atg13 gene and the subsequent autophagy impairment may initiate a series of metabolic changes in myeloid cells. These changes start with the deficit in mitochondrial energy metabolism (confirmed by Seahorse analyses of OXPHOS and glycolysis), then the augmentation of reactive oxygen species ( Mito-ROS assay), then the nifrosylative inactivation of cellular deacetylase enzyme called SIRT1 , which maintains the acetylation status of NF-κB. These series of metabolic changes drive the induction of the inflammatory phenotype in perivascular macrophages. Along with CD40, we examined the impact of atg13-dependent autophagy impairment in the expressions of other surface antigens such as CD86, CD163, and CD206 in the context of inflammatory response in myeloid cells.

Summary: The pathway we describe highlights how NF-kB-mediated inflammatory changes in myeloid cells may contribute to the neurogenic symptoms of muscle fatigue, post-exertional malaise, and potentially post-infectious fatigue syndromes.
@MECFSNews @UWM

[Roy lab @ProfAvikRoy]

Excited to contribute a research with @RedefiningMECFS, @ggottschalkPhD on ATG13's role in chronic fatigue, recently accepted by Inflammation Research of @SpringerNature.. The full paper is under production now. Our research is timely and relevant as another study in Nature Communications (Hu et al. PMID: 41309545) linked  ATG13-binding protein FIP200 in long COVID genetics. @MECFSResearch @PlzSolveCFS @MEResearchUK @UWM