June 13, 2022
Jerome W. Conn Award for Excellence in Research
Awarded to Dr. Hayek by Michigan Medicine's Department of Internal Medicine!
As stated by the Internal Medicine Department Chair, Dr. John Carethers, C. Richard Boland Distinguished University Professor, John G. Searle Professor and Chair - Department of Internal Medicine, and Professor of Human Genetics -
Additional congratulations to the other Conn Awardee for the year, Renuka Tipirneni, MD, MSc.
April 22, 2022
A big JOB WELL DONE to our 2021-2022 undergraduate research students for their year of work and their posters and presentations this week.
We've enjoyed working with our undergraduate mentees through the Undergraduate Research Opportunity Program, and are delighted to have a few returning to work with us through the summer and next fall as Research Assistants. Mentoring a diverse group of individuals towards future physicians and scientists is an incredibly gratifying and valuable endeavor. Take a look at the outcomes of their research projects below.
Postdoctoral Research Fellow Alexi Vasbinder and team drew from a diverse cohort of individuals included in the International Study of Inflammation in COVID-19 (ISIC) to understand the effect of Diabetes Mellitus on primary COVID-19 outcomes through mechanisms of inflammation and hyperglycemia.
The primary outcome of interest among patients with DM was the composite of in-hospital death, need for mechanical ventilation, and renal replacement therapy.
33.5% of participants were characterized to have DM (n = 686). Compared to patients without DM, these participants had a higher incidence of the primary outcome and higher levels of inflammatory biomarkers, namely suPAR.
This study found that suPAR levels accounted for most of the associated risk between diabetes and COVID-19 outcomes. Through mechanisms of hyperinflammation, suPAR mediated 84.2% of the primary COVID-19 outcome in patients with DM.
“Association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation”
December 16, 2021
Drug treatment for COVID-19 requires an understanding of its viral mechanisms and interactions with the human host. The SARS-CoV-2 viral S protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor for entry into the host cell, and viral activation of the ACE2 receptor initiates the pro-inflammatory renin-angiotensin system (RAS) cascade uncontrollably, causing damage to the body. ACE inhibitors (ACEi) and angiotensin receptor blocker (ARB) drugs serve to target this mechanism and have been used previously for treatment of hypertension and heart failure.
Dr. Michael Pan explores the effects of this class of drugs on COVID-19 patients in his newly published paper:
This study is the first of its kind to incorporate highly specific data from patients enrolled in the International Study of Inflammation in COVID-19 (ISIC) and the Michigan Medicine Covid-19 Cohort (M2C2) study. Patients on ACEi/ARB were older and had significant comorbidities like diabetes mellitus, chronic kidney disease, and coronary artery disease as compared to the non-ACEi/ARB patient group. While previous studies analyzing the effects of ACEi/ARB drugs have focused specifically on hypertensive patients, this study saw improved outcomes across all patient subgroups.
The in-hospital treatment group was also found to have lower levels of suPAR and C-reactive protein, lower in-hospital mortality, and lower incidence of need for mechanical ventilation and dialysis compared to patients who did not receive drug treatment.
Potential benefits of ACE/ARB use among COVID-19 patients include an attenuated inflammatory response and lung protective mechanisms as supported by the evidence in this study.
This work focused on characterizing the clinical detail of patients and analyzing its impact on observed disparities. The research team compared differences in inflammatory biomarker measurements, directed therapies, trial enrollments, comorbidities, and specific clinical outcomes. Most significantly, this study found differences in the prevalence of risk factors of patients and the treatment they received.
On average, Black patients hospitalized for COVID-19 were younger, had higher BMI, and disproportionately suffered from conditions like hypertension, diabetes, and chronic kidney disease as compared to non-Black patients. Despite a higher prevalence of these comorbidities and risk factors, Black patients were less likely to enroll in clinical trials and less likely to receive FDA approved COVID-19 therapeutic treatments like remdesivir, corticosteroids, and convalescent serum.
“A complex interplay between social determinants of health and associated comorbidity burden has been posited as the basis for the observed disparities in COVID-19 infection rate”
Azam attributes these differences in patient treatment as a result of racially biased healthcare. Underlying levels of inflammation and the presence of risk factors play a role in the severity of disease, and the data in this study suggests that differential treatment can further exacerbate patients’ clinical outcomes. Historical precedence of inadequate care additionally contributes to the reluctance of patient enrollment in clinical trials. The racial disparities and worse outcomes of Black patients in this study are impacted by preexisting inflammation and suboptimal treatment, and Azam reckons for a reevaluation of our health institutions and systems.
November 30, 2021
Our postdoctoral research fellow Alexi Vasbinder has been working closely to investigate the relationships between inflammation, hyperglycemia and adverse outcomes among patients with Diabetes Mellitus (DM) hospitalized for COVID-19. This study draws from a diverse cohort of individuals included in the International Study of Inflammation in COVID-19 (ISIC) and its largest sub-cohort, the Michigan Medicine Covid-19 Cohort (M2C2).
Analysis of collected data found patients with DM to be older, more likely to be Black, obese, and have a greater burden of comorbidities such as hypertension, coronary artery disease, and heart failure.
Additionally, these patients were found to have higher levels of biomarkers upon admission, including suPAR, CRP, procalcitonin, and D-dimer. Of these, the team identified suPAR to be the most important risk factor. As the only independently associated biomarker associated with diabetes, suPAR mediated 84.2% of composite outcomes of diabetes through inflammatory mechanisms, while worse outcomes were associated with hyperglycemia and higher insulin requirements during hospitalization. Other important risk factors include BMI, admission glucose levels, and age.
October 28, 2021
The Hayek Lab is ecstatic about our latest piece of equipment from Ortho Clinical Diagnostics, the Vitros 3600!
... and we're excited to unpack how it works....
This immunodiagnostic system will measure the inflammatory biomarker levels in patients hospitalized for COVID-19. Identification of certain biomarkers will help analyze the risk of different secondary events beyond initial infection.
September 15, 2021
Kingsley Amadi, a current junior at Michigan State University, joined the Hayek Lab this summer as a laboratory assistant developing ongoing research efforts related to suPAR and the management of multi-vessel coronary artery disease. Patients with this disease generally undergo coronary artery bypass grant (CABG) surgery, yet many of those who do not require a full surgery prefer a less invasive procedure called percutaneous coronary intervention (PCI). Ultimately, this research aims to develop a method in determining whether a patient requires the CABG surgery or the stent procedure.
To work towards this goal, Kingsley’s project focused on understanding the role of suPAR levels as one of the markers of multi-vessel coronary artery disease and deriving appropriate cut-off levels that affect this clinical treatment direction. For this project, the Hayek Lab used samples from BARI-2D, a clinical trial for patients with type 2 diabetes with some cardiac symptoms.
In the lab, Kingsley worked with fellow lab members Chris Launius, Iman Shaikh, and Annika Tekumulla. On a day to day basis, Kingsley tended to the mouse colonies and performed various assays to measure suPAR, 8-isoprostanes, and mouse atherosclerosis biomarkers. Concentration levels of these biomarkers were updated into data sample software Freezerworks and standardized through Softmax Pro computer analysis.
Though the Hayek Lab continues to gather these results, current data has demonstrated suPAR levels ranging from 3 to 6 mg/mL and higher within patients with multi-vessel coronary artery disease, an indication of inflammation. Kingsley remains optimistic about the promising role suPAR plays in disease management and tracking, and the Hayek Lab appreciates his efforts.
Kingsley is now back in East Lansing for the fall semester, and we wish him the best of luck!
September 1, 2021
Over the past year and a half, the Hayek Lab has developed the Michigan Medicine COVID-19 Cohort (M2C2) study consisting of all adult patients hospitalized primarily for COVID-19 at the University of Michigan.
This comprehensive resource has collected biological samples from a large population of patients over the course of their hospitalization.
We Have News!
Read more about the study below!
August 13, 2021
The Hayek Lab received serum samples from the PERL trial at Harvard University. This trial looked at patients with T1DM who had elevated levels of Serum Uric Acid (SUA). SUA is associated with diabetic nephropathy (DN). The suPAR levels of the received samples from the PERL trial were quantified using ELISA (enzyme-linked immunosorbent assay) and ViroGates suPARnostic kits. While typical suPAR levels in individuals are generally less than 3 ng/mL, Iman’s study found elevated suPAR levels in patients with T1DM ranging from 3.01 ng/mL to 9.95 ng/mL. This indicates a correlation between suPAR levels and the progression of illness in patients with T1DM.
Iman worked with fellow team members Chris Lanius, Kingsley Amadi, and Annika Tekumulla to perform ELISA assays and analyze the characteristics and adverse CV events of trial participants by their resulting suPAR values.
In her general study of suPAR, she discovered the significance of this biomarker in a myriad of patient illnesses. Levels of this protein are very elevated and present for people who have most every dangerous CV disease, kidney disease, cancer, and COVID-19. This ubiquity suggests the critical role of suPAR in predicting diseases. As a future medical professional, Iman urgently hopes that suPAR levels are regularly checked during routine blood tests.
In comparison to her other research experiences, Iman enjoyed the immediate clinical applicability of this project.
“It seems like it’s happening really quickly, and it’s just really exciting to me!”
This fall, Iman will be a senior at UCLA studying Microbiology, Immunology, and Molecular Genetics with plans to go to medical school. Searching for a valuable research experience this summer, Iman was grateful for the opportunity to live in Ann Arbor for a few months amid the pandemic. She extends her appreciation to the program coordinators of FCVC-SURF and to the entire lab for their willingness to help and mentorship. Apart from her work in the lab, she spent this summer hanging out with other FCVC Fellows from the program, exploring Ann Arbor, and studying for the MCAT.
July 28, 2021
Rising sophomore Annika Tekumulla spent the past year doing virtual clinical research with the Hayek Lab through the Undergraduate Research Opportunities Program. Despite the remote nature of her work, Annika collaborated closely with Dr. Salim Hayek, Penney Kunkle and, Elizabeth Anderson on her project:
Through their work, they discovered a 9.1% VTE prevalence among the 1065 adult COVID-19 patient population at Michigan Medicine, of which 72% of patients with VTE were men. VTE was found to be associated with worse outcomes among hospitalized COVID-19 patients. Most notably, they identified D-dimer, C-reactive protein (CRP), and Ferritin as three key biomarkers associated with VTE independently of age, BMI, sex, race, and chronic kidney disease (CKD). All three are significant predictors of future VTE status and are markers of tissue destruction!
In addition to her presentation at the UROP Symposium, Annika had the opportunity to present her research to the Internal Medicine department at Michigan Medicine. Through her UROP experience and continued in-lab summer research with suPAR, Annika has realized a new found interest in inflammatory biomarkers, and she hopes to build on her scientific knowledge and analytical skills in the fall.
July 15, 2021
The Hayek Lab is co-investigating kidney related risk factors associated with the SARS-CoV-2 virus through the ongoing KIDCOV study. This study seeks to better understand how COVID-19 affects long-term health of the kidneys and develop preventative measures to minimize any damage. Periodic urine samples will be collected and examined by the lab to compare the kidney health of participants who have received either a positive or negative COVID-19 test result.
The Sarwal group has selected a number of key biomarkers present in urine samples that reflect levels of kidney injury: cell-free DNA (cfDNA, marker of total apoptotic burden), methylated cfDNA (mcfDNA, marker of renal parenchymal injury), clusterin (marker of tubular injury), CXCL10 (marker of renal inflammation), protein (a late marker of glomerular injury), and creatinine (marker of hydration and diurnal variation).
Upon collection, the lab will carry out Kidney Injury Test (KIT) assays on the samples to identify the presence of these biomarkers and assign KIT scores to accurately quantify any kidney damage among voluntary participants.
May 23, 2021
We'd like to extend our warmest welcome to our new Laboratory Assistant, Kingsley Amadi, who began work for the summer just after completing his Sophomore year at Michigan State University. Kingsley has already thrown himself head first into lab work and we have no doubt how much we will appreciate his time and efforts the next several months!
We'd also like to welcome our newest Research Assistant, ToniMarie Catalan - Toni graduated from University of Michigan last year, in the midst of the pandemic, and has jumped into Clinical Research as a Study Coordinator in Cardiology. We're extremely grateful for her addition to our COVID19 patient data collection and look forward to her expansion into her own projects in the future.
Check out their profiles on our Team page!
Our school year Undergraduate Research Opportunity Program student, Annika Tekumulla, finished out her year with a remote project and fantastic presentation on vascular thromboembolism in COVID19. We're all very proud of her research progress!
Annika felt strongly enough about her positive experience to nominate her main mentor, Penney Kunkle, for the UROP Mentor Award. Excellent work to both Annika and Penney!
We're excited to have Annika join us in the lab for the summer months as well.
April 7, 2021
Congratulations to our Project Manager/Research Coordinator/Laboratory Manager, Penney, on being selected as a recipient of the Staff Award for Excellence for the Department of Internal Medicine. This year, as with all things 2021 so far, recipients will have the joy of celebrating via Zoom.
We're HIRING! We're looking for a Full-Time, Temporary Laboratory Assistant with experience in basic lab skills, clerical organization, and database use. This individual will assist with our numerous fast-paced projects, including processing and assaying human and animal specimen.
Please apply ASAP: ttps://careers.umich.edu/job_detail/196616/laboratory_asst_temp
With our first clinical trial slowly emerging from the administration phase into the active trial phase, the lab will soon be expanding further, with the hiring of a Research Nurse and a Research Technician. Keep an eye on this space for the postings!
March 1, 2021
We participated in February's heart month in various ways, including Dr. Hayek's interview with the NeuroNetwork on the link between Heart and Brain health and one of our recent publications, COVID-19 and Diabetes: A Collision and Collusion of Two Diseases, which can be found on the NeuroNet website or YouTube.
Our multi-center STOP-COVID Investigators team continues to publish great work in top tier journals, including last month's article on ECMO use in COVID19 in Intensive Care Medicine and the effects of Prone Positioning on ventillated COVID19 patients, published in Critical Care Medicine.
And we're excited to announce we have begun recruiting for our KIDCOV study, following patients who have tested positive or negative for SARS-CoV-2 with mild symptoms, collecting urine samples over the course of the year to test for markers of kidney damage.
As the COVID-19 pandemic continues, we are excited that Michigan Medicine has joined with Washtenaw County Health Department to increase vaccination efforts of local teachers and school staff. We hope to be working our way towards a more social summer.
February 9, 2021
Take a moment this month to read about the Six Types of Heart Disease and why heart disease is the leading cause of death as reported by TheHealthy.com. The article includes important information on risk factors and symptoms by Dr. Hayek, including those symptoms specific to women, and tips on prevention by Dr. Janet Wei, a cardiologist at Smidt Heart Institute at Cedars-Sinai Hospital in Los Angeles, California.
Our continued collaboration as the STOP-COVID Investigators has produced another high impact article, Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID19, published earlier this month in Intensive Care Medicine. This study finds that patients with severe hypoxia who received ECMO in the first seven days of ICU admission had lower in-hospital mortality than patients who did not.
November 16, 2020
We have been excited to participate in the 2020 American Heart Association virtual Scientific Sessions conference.
We are fortunate to have several poster presentations in the conference, and want to share them with anyone who was unable to attend.
We thank all of our hardworking research team members and our collaborators for projects started, continued, or completed in what has been a difficult year for everyone.
And many congratulations to Dr. Hayek for receiving the Sarns Innovative Excellence Award from the American Heart Association for helping build a world of longer, healthier lives.
November 2, 2020
Enormous congratulations to Dr. Hayek on his new Endowed Chair position!
Dr. Hayek was awarded the Juanita Murchant, MD PhD, Early Career Endowment Chair through the Department of Internal Medicine at Michigan Medicine. The Department of Internal Medicine initiated the creation of these competitive Early Career Endowment awards in 2019, assigned to junior faculty at the Assistant Professor level to be held by the awardee for 5 years.
Meanwhile, another STOP-COVID original research article, Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19 has been published in JAMA Internal Medicine, to significant international attention.
Early Career Endowment Awards
October 6, 2020
Our amazing research team has clocked a lot of overtime this year extracting data on the course of every COVID19 patient to go through Michigan Medicine. We've created and joined multiple collaborative teams and compiled data and resources to get the best answers fastest. Our newest article really shows the value of the hard work and collaborations, published September 30 in The BMJ.
Using the STOP-COVID database including over 5000 ICU patients in 68 US hospitals, our team found that approximately one in seven patients experienced in-hospital cardiac arrest, of whom only 57% received cardiopulmonary resuscitation. Among those who received cardiopulmonary resuscitation, only 12% survived to hospital discharge, and only 7% did so with normal or mildly impaired neurological status. Survival to hospital discharge varied considerably by age, from 21% in patients younger than 45 years to 2.9% in patients aged 80 and older. Most patients who survived to hospital discharge required only a short course of cardiopulmonary resuscitation.
Our study data could help inform patients, family members, and clinicians in complex decision making about patients with covid-19 who are at risk of cardiac arrest or who have experienced cardiac arrest.
September 24, 2020
We've got a lot of big lab news to announce!
We've hired a new research technician to join our team, Chris Launius! Chris is moving back to his home state of Michigan to join his fiancée who has recently begun a PhD program in the area. Chris received his undergraduate degree from Eastern Michigan University in Biology with a minor in Chemistry. He has mostly recently been working at Northwestern University in Chicago where he assisted in Alzheimer's disease research using mouse models. Prior to Northwestern, Chris had another position at the University of Michigan in the Central Biorepository, from whom we have heard many good things. We're excited to throw Chris into the mix and somehow manage training through all of our COVID19 restrictions!
Our COVID19 research continues at a relentless pace - we're proud to announce our newest article published in the Journal of American Society of Nephrology this month - Soluble Urokinase Receptor (SuPAR) in COVID-19–Related Acute Kidney Injury.
Nearly half of hospitalized patients with coronavirus disease 2019 (COVID-19) develop AKI, with 20% requiring dialysis. We've previously found high levels of soluble urokinase plasminogen activator receptor (suPAR)—an immune mediator of kidney injury— to predispose patients to AKI in various clinical scenarios, including critical illness. In our multicenter observational study, we measured plasma suPAR in 352 patients with COVID-19 within 48 hours of their hospitalization. suPAR levels are strongly associated with incident AKI, independent of such clinical characteristics as kidney function and inflammatory biomarkers, and predictive of the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.
You can check out the full article on JASN's website.
August 19, 2020
We're looking for BOTH a post-doctoral fellow with a background in clinical research interested in biomarker, risk prediction, observational studies and clinical trials, and a laboratory technician with 2-3 years of experience in molecular labwork and animal experimentation.
Our lab’s research activities span the spectrum from bench to bedside, with numerous translational and clinical research projects. Our translational research focuses on understanding the role of soluble urokinase plasminogen activator receptor (suPAR) in kidney and cardiovascular disease. We have an interest in Cardio-Oncology, notably in exploring the role of biomarkers to refine the risk prediction of cardiotoxic effects of chemotherapy. We have lately focused on understanding inflammation in COVID-19 and have created the Michigan Medicine COVID-19 cohort in which we have collected clinical data and measured numerous inflammatory biomarkers.
We are a highly active lab with numerous high yield projects with high impact publications.
Check out our job postings here -
July 8, 2020
We have exciting news this summer in the Hayek Lab! First and foremost, Dr. Hayek has been appointed to the position of Medical Director of the Frankel Cardiovascular Center Clinic Ambulatory Care Unit. Dr. Hayek plans on taking a data driven approach, leveraging technology to add improvements to the next phase of ambulatory care at Michigan Medicine.
Funding for our R01 provided through NHLBI has arrived and we’re excited to continue on with work examining the role of the circulating immune-derived glycoprotein, suPAR, in cardiovascular and kidney diseases. This 5 year project will allow us to delve much deeper into suPAR as a potential pathogenic factor for cardiovascular disease, and drive the future of preventative interventions. Preliminary data for the project was supported by two separate pilot grants here at the University of Michigan, whose support we were grateful to have.
For World Refugee Day on June 20, Dr. Hayek was interviewed by the NeuroNetwork for Emerging Therapies, a research group focused on creating cures that Dr. Hayek recently joined. You can read the brief article online.
June 2, 2020
With an amazing 4 project proposal grant submissions in the past month, the Hayek lab has been busy. Data collection and biomarker assays have continued for our COVID-19 research projects, and we’re looking to begin manuscript writing in earnest this month as we analyze data and interpret results. We’re excited to be able to disseminate information from the many projects we’ve been working on and hope to post manuscript links soon!
We are also excited to slowly ramp up non-COVID19 bench research at UM, as public health considerations and regulations from the state of Michigan have allowed with the decreasing number of COVID-19 cases in the state. Labwork is being phased in over the course of the summer across UM campuses, more research space opening as each phases is deemed successful and difficulties are sorted out. We're looking to the future and hopeful for a productive and expansive second half the year.
May 1, 2020
Dr. Hayek and his lab have begun several projects working towards increased understanding of our current global health crisis: COVID19. Along with researchers across the United States and several countries in Europe, we are beginning to look into various aspects of the SARS-CoV-2 infection, including clinical presentation, triaging, blood and urine biomarkers, and outcomes generally and in several long-term disease categories. Biosafety level 2 labwork and data collection are well underway as we race to find therapies that will help before the next wave of this pandemic roles through. More information about our studies, including our M2C2 dataset can be found on our COVID19 Research page.