Dr. Rayees earned his PhD degree from CSIR-IIIM and SMVDU and conducted his postdoctoral research work at University of Illinois Chicago, USA. During his postdoctoral research he studied i) the counterbalancing mechanism that deactivates alveolar macrophage inflammatory signalling to prevent lethal lung edema, and ii) the signalling cascade that activates P. aeruginosa clearance in alveolar macrophages to prevent death from bacterial pneumonia.

He demonstrated that PAR2, a GPCR, induced cAMP generation in alveolar macrophages and suppresses activation NFAT, secondary to Ca²⁺ entry through TRPV4 channel and hence blocks the inflammatory signalling of alveolar macrophages which may otherwise lead to lethal pulmonary edema.

In another study, he showed that PAR2 expressed on mouse alveolar macrophages mediates the clearance of P. aeruginosa to prevent mortality from pneumonia. He showed that binding of P. aeruginosa to PAR2 elevated cAMP levels, activates Rac1 through PKA to form actin-rich protrusions and augment clearance of P. aeruginosa. These studies involved the use of highly efficient mouse models such as generation of mouse chimeras (bone marrow transplantation), in vivo gene delivery of PAR2, CREB, Rac1 (Q61L) cDNA   in inflammation, infection and developmental biology mice models, adoptive transfer of PAR2^+/+ or PAR2^-/- and macrophages following clodronate induced macrophage depletion and mouse models of bacterial pneumonia. These studies also involved use of explicit cell biology techniques related to GPCR translocation, FRET imaging, live cell imaging, electroporation.

His scientific training during PhD programme at CSIR-IIIM was mainly focussed on drug discovery. He published several good impact research articles as lead author. During this tenure he learnt techniques related to general and advanced pharmacology, pharmacokinetics and pharmacodynamics. He gained special expertise over rodent invasive and non-invasive techniques during his PhD programme.

Recently Dr. Rayees demonstrated that TRPV4 activation increases intracellular Ca²⁺, activating CREB to boost IL-10 production in macrophages, which helps reprogram them to resist inflammatory damage. In a mouse ALI model, TRPV4-driven IL-10 did not resolve inflammation but prevented mitochondrial dysfunction via the CREB-IL-10 axis. IL-10 also promoted mitophagy, clearing damaged mitochondria in LPS-exposed cells. The study suggested TRPV4 and IL-10 as potential targets for mitigating inflammation-related cellular dysfunction.