On this #OMFScienceWednesday we are pleased to introduce you to a central member of the OMF-funded ME / CFS Collaborative Research Center team at the Stanford Genome Technology Center (SGTC), Mohsen Nemat-Gorgani, PhD. Dr. Nemat-Gorgani is leading a team to investigate the Red Blood Cells (RBC) in ME / CFS patients. Mohsen shared his story with OMF.

“I was born and raised in Iran and did my undergraduate and graduate studies in U.K. In 1974, I obtained a PhD in biochemistry from Warwick University, and after a year of postdoctoral training at Vanderbilt, I returned to Iran. In October 2003, I came to the Stanford Genome Technology Center (SGTC) as a Visiting Professor from Tehran University and continued working as a Research Associate upon termination of the sabbatical leave. During my time at the Center, I participated in various technology development projects, and about two years ago, after a brief absence from the Center, I started working on ME / CFS.

Upon participation in the ME / CFS project, and during the first few months of my presence at the Center, I learnt, mainly by talking to Ron Davis, Laurel Crosby and a number of patients, that inadequate blood flow to tissues could be the cause of some of the symptoms reported in ME / CFS. It also became known to me that red blood cells (RBCs) and their mechanical properties may largely determine the rheological (deformation and flow) behavior of blood in normal and disease states.

Interestingly, a few years before working on ME / CFS, I was somewhat involved in a study on the mechanical properties of breast cancer cells at the Center. This work was conducted by Shane Crippen, a graduate student under the guidance of Ron Davis, Roger Howe and Stefanie Jeffrey (Electrical Engineering and Stanford Medical School, respectively). In the course of subsequent discussions (in June 2016) with Ron and Roger, it was decided that we should look at the mechanical properties of RBCs related to ME / CFS, and we started exploring different technical approaches to achieve this goal.

In January 2017, during a visit to SJSU, I met Anand Ramasubramanian who had recently taken up a faculty position in the Chemical and Materials Engineering Department. Anand had previously looked at deformability of monocytes using a microfluidic platform, and during the course of our discussions, it became obvious that a collaboration with his team (involving Amit Saha, who had worked with Anand on monocyte deformability as a part of his Ph.D. thesis, and graduate students) would be an effective way of going forward. A few months later, the studies were initiated, and with the outstanding technical support provided by Julie Wilhelmy and Layla Cervantes, samples from a large number (over 30) of ME / CFS patients and healthy controls were collected at the SGTC, and later analyzed at SJSU.

RBC deformability is believed to play an important role in their main function – the transport of oxygen and carbon dioxide via blood circulation. They are highly elastic, which allows them to flow easily. The reason for this exceptional property is found in the composition of the membrane and the membrane-cytoskeleton interaction. A healthy RBC is approximately 8.0 µm in diameter, which needs to undergo large deformations in order to pass through capillaries, around 2-3 µm in diameter. A slight decrease in deformability has been shown to cause a significant increase in microvascular flow resistance, with important physiological implications.

RBC deformability has been shown to be impaired in various pathologies including inflammatory conditions such as sepsis. Recent studies have clearly indicated that inflammation is involved in ME / CFS. Moreover, RBCs are highly susceptible to oxidative stress due to the high contents of polyunsaturated fatty acids in the cell membrane, a process that may impair deformability, and some studies have indicated RBC oxidative damage occurring in ME / CFS.

Using the microfluid platform, the mechanical properties of RBCs from ME / CFS and healthy control samples have been compared by determination of the time taken to enter the channels as well as transit velocity, and elongation capacity. Our preliminary results suggest clear differences in deformability of RBCs from ME / CFS and healthy control blood samples using this platform. A manuscript has recently been submitted for publication describing these observations.

Studies underway include biochemical analyses, membrane fluidity determination, lipidomics analysis, atomic force microscopy (AFM), scanning electron microscopy, zeta potential and simulation studies.

In recent months, we have established collaborations with other groups including the following:

Andrey Malkovskiy, PhD, Stanford School of Medicine, and the Stanford Nano Shared Facilities (AFM studies). Vinny Chandran Suja, graduate student, Chemical Engineering, Stanford (zeta potential studies). Eric Shaqfeh, PhD, Professor, and Amir Saadat, Postdoctoral Scholar, Chemical Engineering, Stanford (simulation studies).

The zeta potential and related studies are expected to be in collaboration with Gerald Fuller’s group (Professor, Chemical Engineering, Stanford).

Financial support for all these efforts has been provided by OMF. It is hoped that differences in RBC mechanical properties will serve as a label-free biomarker in CFS diagnosis. We hope the described collaborative efforts will help us develop a diagnostic device for ME / CFS.

It is a great pleasure and privilege to be part of Ron’s team, and to try to contribute toward solving the mystery of ME / CFS.“

Thank you, Mohsen for providing us with a detailed look into the potential effects of RBC alterations and for leading a stellar team. We sincerely appreciate your work with Dr. Davis.