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Two separate findings by a University of Houston nationally recognized expert in systemic lupus erythematosus (SLE or lupus), a chronic autoimmune disease that affects multiple organs including the kidneys, skin, joints and heart, are being reported in scientific and medical journals.
Chandra Mohan, M.D., Ph.D., Hugh Roy and Lillie Cranz Cullen Endowed Professor of biomedical engineering in the UH Cullen College of Engineering, has identified blood biomarkers that predict which lupus patients will develop heart disease in the future and found new urine biomarkers for diagnosing lupus nephritis (LN) in children with lupus.
Lupus and Cardiovascular Disease
Lupus is associated with an increased incidence of acute and chronic cardiovascular disease as compared to the general population.
Mohan’s team, in collaboration with Dr. Maureen McMahon at UCLA, used a comprehensive metabolomic screen of baseline sera from lupus patients to identify metabolites that predict future carotid plaque progression, following eight to nine years of follow-up. Nine patients had SLE without plaque progression, eight had SLE and went on to develop atherosclerotic plaques, and eight patients were controls who did not have SLE.
“The arachidonic acid pathway metabolites, leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE), and the oxidized lipids 9/13-hydroxyoctodecadienoic acid (HODE) were found to be significantly altered (p < 0.05 and fold-change >2) in SLE patients compared to SLE patients without plaque progression,” reports Mohan in Frontiers in Cardiovascular Medicine. “SLE patients also exhibited significantly altered levels of branched chain amino acid (BCAA) metabolites and plasmalogens compared to the non-SLE controls.”
Taken together with the rich literature on these metabolites, the findings suggest that the identified metabolites may not only be prognostic of cardiovascular disease development in SLE patients, but they may also be active drivers of atheroma formation. Early identification of these high risk SLE patients may help institute preventive measures early in the disease course.

The Age-Related Eye Disease Studies (AREDS and AREDS2) established that dietary supplements can slow progression of age-related macular degeneration (AMD), the most common cause of blindness in older Americans. In a new report, scientists analyzed 10 years of AREDS2 data. They show that the AREDS2 formula, which substituted antioxidants lutein and zeaxanthin for beta-carotene, not only reduces risk of lung cancer due to beta-carotene, but is also more effective at reducing risk of AMD progression, compared to the original formula. A report on the study, funded by the National Institutes of Health, published in JAMA Ophthalmology.
“Because beta-carotene increased the risk of lung cancer for current smokers in two NIH-supported studies, our goal with AREDS2 was to create an equally effective supplement formula that could be used by anyone, whether or not they smoke,” said Emily Chew, M.D., director of the Division of Epidemiology and Clinical Application at the National Eye Institute (NEI), and lead author of the study report. “This 10-year data confirms that not only is the new formula safer, it’s actually better at slowing AMD progression.”
AMD is a degenerative disease of the retina, the light-sensitive tissue at the back of the eye. Progressive death of retinal cells in the macula, the part of the retina that provides clear central vision, eventually leads to blindness. Treatment can slow or reverse vision loss; however, no cure for AMD exists.
The original AREDS study, launched in 1996, showed that a dietary supplement formulation (500 mg vitamin C, 400 international units vitamin E, 2 mg copper, 80 mg zinc, and 15 mg beta-carotene) could significantly slow the progression of AMD from moderate to late disease. However, two concurrent studies also revealed that people who smoked and took beta-carotene had a significantly higher risk of lung cancer than expected.
In AREDS2, begun in 2006, Chew and colleagues compared the beta-carotene formulation to one with 10 mg lutein and 2 mg zeaxanthin instead. Like beta-carotene, lutein and zeaxanthin are antioxidants with activity in the retina. The beta-carotene-containing formation was only given to participants who had never smoked or who had quit smoking.
At the end of the five-year AREDS2 study period, the researchers concluded that lutein and zeaxanthin did not increase risk for lung cancer, and that the new formation could reduce the risk of AMD progression by about 26%. After the completion of the five-year study period, the study participants were all offered the final AREDS2 formation that included lutein and zeaxanthin instead of beta-carotene.
In this new report, the researchers followed up with 3,883 of the original 4,203 AREDS2 participants an additional five years from the end of the AREDS2 study in 2011, collecting information on whether their AMD had progressed to late disease, and whether they had been diagnosed with lung cancer. Even though all the participants had switched to the formula containing lutein and zeaxanthin after the end of the study period, the follow up study continued to show that beta-carotene increased risk of lung cancer for people who had ever smoked by nearly double. There was no increased risk for lung cancer in those receiving lutein/zeaxanthin. In addition, after 10 years, the group originally assigned to receive lutein/zeaxanthin had an additional 20% reduced risk of progression to late AMD compared to those originally assigned to receive beta-carotene.
“These results confirmed that switching our formula from beta-carotene to lutein and zeaxanthin was the right choice,” said Chew.
The study was funded by the NEI Intramural program (EY000546) and through contracts (AREDS2 contract HHS-N-260-2005-00007-C; ADB contract NO1-EY-5-0007; AREDS Contract NOI-EY-0-2127, and contract HHS-N-263-2013-00005-C). The AREDS2 contracts were supported by the NIH Office of Dietary Office of Dietary Supplements, the National Center for Complementary and Alternative Medicine, the National Institute on Aging, the National Heart, Lung, and Blood Institute, and the National Institute of Neurological Disorders and Stroke. The study took place at the NIH Clinical Center.
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Genetically engineered immune cells successfully target the specific cancer cells that may be responsible for relapse of acute myeloid leukemia (AML), a type of blood cancer, and proved effective in animal models of the disease, according to a preclinical study by investigators at Weill Cornell Medicine. The new cell therapy, now being tested in phase 1 clinical trials, may ultimately help patients with AML to remain cancer-free.
In the study, published April 28 in Nature Communications, the researchers used an approach in which immune cells known as T cells are directed to produce proteins called chimeric antigen receptors, or CARs, that enable the T cells to recognize specific markers on cancer cells. In this case, the CAR is a receptor that binds to the CD123 molecule on leukemia stem cells, enabling the T cells to seek out and attack the cancer cells.
“Leukemia stem cells are a subset of leukemic cells that are resistant to standard chemotherapy drugs and can cause disease relapse,” said co-senior author Dr. Monica L. Guzman, associate professor of pharmacology in medicine in the Division of Hematology & Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “CD123 is a marker found on leukemia stem cells, and my laboratory has been working on designing mouse models to test new CD123-targeted anti-leukemia therapies.”
Although there are effective therapies to treat AML, the disease eventually recurs in most patients even after achieving complete remission. By engineering T cells to express a CAR that targets CD123, Dr. Guzman and her colleagues hope to rid patients of any remaining leukemia stem cells. CAR T cells are an attractive anti-cancer therapy because they can be grown in large numbers in the laboratory.
“The CAR T cells — called UCART123 cells — used in this study have several very important features,” said Dr. Guzman. “They target a leukemia stem cell marker, they are derived from healthy donors and manufactured to be ‘off the shelf’ and ready-to-go for patients when needed, they are specially designed to try to minimize toxicity, and they can be eliminated using a drug called rituximab in case of excessive proliferation.”
When the team tested the UCART123 cells in a mouse model of AML, they found that the therapy effectively eliminated leukemia cells and prolonged survival. The scientists also designed an ultra-sensitive monitoring strategy to detect any residual cancer cells and to assess the persistence of UCART123 cells. Finally, they demonstrated that UCART123 cells have specificity against leukemia cells, with minimal toxicity to normal blood cells in mice.
The preclinical results have led to a phase 1 clinical trial testing UCART123 in patients with relapsed/refractory AML at several sites across the United States, including NewYork-Presbyterian/Weill Cornell Medical Center. “These laboratory data strongly support the ongoing clinical trial,” said trial principal investigator and senior co-author Dr. Gail Roboz, director of the Clinical and Translational Leukemia Program at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
“The results of the preclinical study suggest that UCART123 cells are highly selective and specific in targeting AML, and we anticipate that the techniques developed in Dr. Guzman’s lab will help us monitor patients undergoing treatment with UCART123 and optimize their likelihood of success,” said Dr. Roboz, who is also professor of medicine in the Division of Hematology & Medical Oncology and a member of the Meyer Cancer Center at Weill Cornell Medicine.
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Researchers have developed an enhanced version of optical coherence tomography (OCT) that can image biomedical samples at higher contrast and resolution over a wider 3D field of view than was previously possible. The new 3D microscope could be useful for biomedical research and eventually enable more accurate medical diagnostic imaging.
In Optica, Optica Publishing Group’s journal for high-impact research, the researchers from Duke University describe the new technique, which they call 3D optical coherence refraction tomography (3D OCRT). Using various biological samples, they show that 3D OCRT produces highly detailed images that reveal features difficult to observe with traditional OCT.
OCT uses light to provide high-resolution 3D images without requiring any contrast agents or labels. Although it is commonly used for ophthalmology applications, the imaging method can also be used to image many other parts of the body such as the skin and inside the ears, mouth, arteries and gastrointestinal tract.
“OCT is a volumetric imaging technique widely used in ophthalmology and other branches of medicine,” said first author Kevin C. Zhou. “We developed a new and exciting extension, featuring novel hardware combined with a new computational 3D image reconstruction algorithm to address some well-known limitations of the imaging technique.”
“We envision this approach being applied in a wide variety of biomedical imaging applications, such as in vivo diagnostic imaging of the human eye or skin,” said research team co-leader Joseph A. Izatt. “The hardware we designed to perform the technique can also be readily miniaturized into small probes or endoscopes to access the gastrointestinal tract and other parts of the body.”
Seeing more with OCT
Although OCT has proven useful both in clinical applications and biomedical research, it is difficult to acquire high-resolution OCT images over a wide field of view in all directions simultaneously due to fundamental limitations imposed by optical beam propagation. Another challenge is that OCT images contain high levels of random noise, called speckle, which can obscure biomedically important details.

As prices for genetic testing go down and awareness of what these tests can do goes up, more and more people are choosing to have their DNA analyzed. One limitation to these tests is that even when they are conducted with guidance from a doctor, genetic variants may be detected whose roles in disease risk are not fully understood. In a commentary published on June 2 in the American Journal of Human Genetics, researchers examined how these “variants of uncertain significance” (VUS) can be introduced by underrepresentation of certain ancestry groups — as well as ways to reduce their incidence in genetic databases.
“A great deal of effort goes into broad-based projects that aim to recruit diverse segments of the population,” says first author Paul Appelbaum, director of the Center for Research on Ethical, Legal & Social Implications of Psychiatric, Neurologic & Behavioral Genetics at Columbia University. “What’s different about our contribution here is the recognition that broad-based recruitment will need to be complemented by more focused efforts that take group concerns into account.”
There are a number of practical and ethical reasons that VUS are important to address. Tests that yield a VUS fail to generate information that is useful clinically. Additionally, although current guidelines discourage clinicians from making treatment decisions on the basis of a VUS, many clinicians and patients may feel compelled to act on them anyway. Discovery of a VUS can lead to anxiety, distress — especially variants in genes known to increase the risk of diseases like cancer — and, in some cases. even drastic interventions like prophylactic surgery.
In this paper, the investigators focused on particular cultural issues among two ancestry groups, as well as culturally informed ways to address and overcome those issues.
For the first group — the Sephardi Jewish community in New York — they used data collected by the Dor Yeshorim project, an effort created to reduce the incidence of genetic diseases in the Jewish community, especially Tay Sachs. The second group was the Silent Genomes Project, an effort housed at the University of British Columbia that aims to reduce healthcare disparities and improve diagnostic success for children with genetic diseases from Indigenous populations in Canada.
“Both of these groups have specific cultural reasons for being hesitant to provide genetic data. By working with them to find ways to address their concerns, we can overcome these hesitations,” Appelbaum says.
Appelbaum acknowledges challenges in scaling up these kinds of efforts to reach other underrepresented populations and the lack of a one-size-fits-all approach. “For each of these groups, we need to recognize the reasons for their underrepresentation and work with them to find ways to address those concerns,” Appelbaum says. He adds that it’s vital to obtain more funding for targeted recruitment efforts and to develop a governance structure that involves the relevant communities in an ongoing fashion.
“It’s crucial to know the frequency of variants in the population,” Appelbaum says. “And given differences in variant frequency across population groups and the prevalence of population-specific variants, comparisons with reference data from a specific ancestral group may be crucial. That’s true in both clinical settings and in research.”
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A breakdown in how brain cells rid themselves of waste precedes the buildup of debris-filled plaques known to occur in Alzheimer’s disease, a new study in mice shows.
The field argued for decades that such plaques, containing the protein amyloid beta, built up outside of cells as a crucial first step toward the brain damage observed in Alzheimer’s disease. Led by researchers at NYU Grossman School of Medicine and the Nathan Kline Institute, the new study challenges this idea, known as the amyloid cascade hypothesis.
The lastest study findings argue instead that neuronal damage characteristic of Alzheimer’s disease takes root inside cells and well before these thread-like amyloid plaques fully form and clump together in the brain.
Publishing as the cover article in the journal Nature Neuroscience online June 2, the study traced the root dysfunction observed in mice bred to develop Alzheimer’s disease to the brain cells’ lysosomes. These are small sacs inside every cell, filled with acidic enzymes involved in the routine breakdown, removal, and recycling of metabolic waste from everyday cell reactions, as well as from disease. Lysosomes are also key, researchers note, to breaking down and disposing of a cell’s own parts when the cell naturally dies.
As part of the study, researchers tracked decreasing acid activity inside intact mouse cell lysosomes as the cells became injured in the disease. Imaging tests developed at NYU Langone Health and Nathan Kline (to track cellular waste removal) showed that certain brain cell lysosomes became enlarged as they fused with so-called autophagic vacuoles filled with waste that had failed to be broken down. These autophagic vacuoles also contained earlier forms of amyloid beta.
In neurons most heavily damaged and destined for early death as a result, the vacuoles pooled together in “flower-like” patterns, bulging out from the cells’ outer membranes and massing around each cell’s center, or nucleus. Accumulations of amyloid beta formed filaments inside the cell, another hallmark of Alzheimer’s disease. Indeed, researchers observed almost-fully formed plaques inside some damaged neurons.

If you need another reason to start the day drinking a cup of joe, a recent study by Johns Hopkins Medicine researchers has revealed that consuming at least one cup of coffee a day may reduce the risk of acute kidney injury (AKI) when compared to those who do not drink coffee.
The findings, published May 5 in the journal Kidney International Reports, show that those who drank any quantity of coffee every day had a 15% lower risk of AKI, with the largest reductions observed in the group that drank two to three cups a day (a 22%-23% lower risk).
“We already know that drinking coffee on a regular basis has been associated with the prevention of chronic and degenerative diseases including type 2 diabetes, cardiovascular disease and liver disease,” says study corresponding author Chirag Parikh, M.D., Ph.D., director of the Division of Nephrology and professor of medicine at the Johns Hopkins University School of Medicine. “We can now add a possible reduction in AKI risk to the growing list of health benefits for caffeine.”
AKI, as described by the National Kidney Foundation, is a “sudden episode of kidney failure or kidney damage that happens within a few hours or a few days.” This causes waste products to build up in the blood, making it hard for kidneys to maintain the correct balance of fluids in the body.
AKI symptoms differ depending on the cause and may include: too little urine leaving the body; swelling in the legs and ankles, and around the eyes; fatigue; shortness of breath; confusion; nausea; chest pain; and in severe cases, seizures or coma. The disorder is most commonly seen in hospitalized patients whose kidneys are affected by medical and surgical stress and complications.
Using data from the Atherosclerosis Risk in Communities Study, an ongoing survey of cardiovascular disease in four U.S. communities, researchers assessed 14,207 adults recruited between 1987 and 1989 with a median age of 54. Participants were surveyed seven times over a 24-year period as to the number of 8-ounce cups of coffee they consumed per day: zero, one, two to three, or more than three. During the survey period, there were 1,694 cases of acute kidney injury recorded.
When accounting for demographic characteristics, socioeconomic status, lifestyle influences and dietary factors, there was a 15% lower risk of AKI for participants who consumed any amount of coffee versus those who did not. When adjusting for additional comorbidities — such as blood pressure, body mass index (BMI), diabetes status, use of antihypertensive medication and kidney function — individuals who drank coffee still had an 11% lower risk of developing AKI compared with those who did not.
“We suspect that the reason for coffee’s impact on AKI risk may be that either biologically active compounds combined with caffeine or just the caffeine itself improves perfusion and oxygen utilization within the kidneys,” says Parikh. “Good kidney function and tolerance to AKI — is dependent on a steady blood supply and oxygen.”
More studies are needed, Parikh says, to define the possible protective mechanisms of coffee consumption for kidneys, especially at the cellular level.
“Caffeine has been postulated to inhibit the production of molecules that cause chemical imbalances and the use of too much oxygen in the kidneys,” he explains. “Perhaps caffeine helps the kidneys maintain a more stable system.”
Parikh and his colleagues note that coffee additives such as milk, half-and-half, creamer, sugar or sweeteners also could influence AKI risks and warrant further investigation. Additionally, the authors say that consumption of other types of caffeinated beverages, such as tea or soda, should be considered as a possible confounding factor.
Other researchers involved in this study include Emily Hu, Elizabeth Selvin and Josef Coresh from the Johns Hopkins Bloomberg School of Public Health; Morgan Grams from the Johns Hopkins School of Medicine; Casey Rebholz from the Johns Hopkins Medicine and Bloomberg School of Public Health Kalie Tommerdahl and Peter Bjornstad from the University of Colorado Anschutz Medical Campus and Lyn Steffen from the University of Minnesota School of Public Health.

Scientists have long known that cocaine works by latching on to molecular connectors on the surface of brain cells, allowing dopamine, a chemical that promotes feelings of pleasure and reward, to accumulate in the space between brain cells. Now, Johns Hopkins Medicine scientists say they have found a molecular connector, known as the BASP1 receptor, that binds cocaine, even when the drug is present in very low doses.
The study, conducted in mice and laboratory-grown mouse brain cells, suggests that blocking the BASP1 receptor may reduce the stimulant effect of cocaine, but only in male mice, not in females, maybe due to the stronger presence of estrogen hormone in the females.
A report on the research was published in the April 19 issue of the Proceedings of the National Academy of Sciences.
Experts have long concluded that cocaine essentially acts as a plug, connecting to brain cells via a molecular “receptor,” and stopping brain cells from sucking in dopamine chemicals through a strawlike structure called a transporter. All of this happens in the space where two brain cells meet and trade chemicals — a synapse. When dopamine fills up a synapse and isn’t absorbed by brain cells, feelings of reward and pleasure last longer.
Scientists have already identified several such transporters and receptors associated with cocaine, but all of them require moderate to high doses of cocaine to effectively link. The Johns Hopkins Medicine team, led by the study’s first author, Maged Harraz, M.B.B. Ch., M.Sc., Ph.D., aimed to find a receptor capable of binding cocaine at low doses. Harraz is an instructor of neuroscience at the Johns Hopkins University School of Medicine.
To do that, Harraz and his colleagues first added cocaine to mouse brain cells in laboratory culture dishes. Then, he ground down the cells, looking for molecules that bound to cocaine. At a concentration of 7 nanomolar of cocaine, an amount that does not engage any known receptor for cocaine, Harraz found the drug bound to the BASP1 receptor.

Mount Sinai researchers have validated for the first time that a simple blood test called a liquid biopsy could be a better predictor of whether cancer immunotherapy will be successful for a patient with lung cancer than an invasive tumor biopsy procedure. Their study was published in the Journal of Experimental & Clinical Cancer Research in June.
The liquid biopsy tests for a biomarker of PD-L1, a protein and target for a type of immunotherapy called checkpoint inhibitors, which helps the patient’s immune system attack and kill cancer cells. This study showed that testing the blood of lung cancer patients for the PD-L1 biomarker gave more accurate predictions of the response and survival for patients with lung cancer than testing for PD-L1 in tissue from lung cancer biopsies, the current standard of care.
The biomarker in blood, named EV PD-L1, comes from extracellular vesicles, which are particles shed from tumor cells. A decrease of PD-L1 in extracellular vesicles in blood could therefore become a useful test to predict which patients with non-small-cell lung cancer could benefit from immunotherapy.
“These results will have an impact in the search for biomarkers to predict for immunotherapy outcome in patients with lung cancer as no truly reliable biomarkers have been found yet,” said senior author Christian Rolfo, MD, PhD, MBA, Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine at Mount Sinai, Associate Director for Clinical Research in the Center for Thoracic Oncology at The Tisch Cancer Institute, and President of the International Society of Liquid Biopsy. “If validated in larger prospective cohorts of patients, as we are working on now, this protein could complement or substitute for the tissue PD-L1 as the standard of care in these and other types of tumor patients receiving immunotherapy, especially because it is minimally invasive and can be repetitive during treatment, being able to detect changes in the tumor during the treatment in real time.”
Researchers collected blood samples from two cohorts of 33 and 24 patients with non-small-cell lung cancer receiving immune-checkpoint inhibitors before and at the ninth week of treatment. They also included a group of 15 patients receiving chemotherapy as controls. Extracellular vesicles were isolated from blood samples and the protein expression of PD-L1 was measured in each group at both time points. Researchers also measured imaging scans of patients’ tumors before treatment and evaluated them with an innovative imaging technology called radiomics to create a full model for prediction of immunotherapy response.
This study, led by Dr. Rolfo, included collaboration of experts in radiomics and medical oncology from the United States, Mexico, and Italy.
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Modern humans are characterized by their prosociality, a broad term that encompasses intraspecies empathy, social tolerance, cooperation and altruism. These facets of social cognition have been associated with variations in the oxytocin and vasotocin genes (OT and VT) and their receptors (OTR and VTR).To shed light on the genetic basis of this behaviour, scientists from the University of Barcelona (UB) and Rockefeller University carried out a new study comparing the available genomic sequences of these genes between modern humans, non-human primate species (e.g., chimpanzees, bonobos, and macaques) and, for the first time, archaic humans, using all the available genomes of Neanderthals and Denisovans.
In the study, published in the journal Comprehensive Psychoneuroendocrinology, the researchers identified several sites in which modern humans differed from both archaic humans and non-human primates, and others where both modern and archaic humans differed from non-human primates.
“We used an interdisciplinary approach to understand the evolution of hominid prosociality through the lens of the oxytocin and vasotocin receptors, where we combined evidence from modern and archaic genomics, population genetics, transcriptomics, and behavioural and neuroscientific studies, among other methods. These results can shed light on the genetics underlying possible sociality differences identified between modern humans and archaic humans, as well as the similarities between the modern human and bonobo social behaviour,” said first author Constantina Theofanopoulou. This research is part of her doctoral thesis carried out under the co-supervision of Cedric Boeckx, ICREA researcher at the Institute of Complex Systems at the UB (UBICS) and Erich D. Jarvis, professor at Rockefeller University.
Variants unique to modern humans in more than 70% of the population
Considering the evidence on modern human prosociality and on the involvement of the oxytocin and vasotocin genes in social behaviours, the researchers hypothesized that the evolution of these genes might elucidate the genetic basis of the evolution of hominin prosociality. With this aim in mind, the study explored the differences between modern humans, archaic humans and non-human primates in polymorphic heterozygous sites in the human genome — locations where at least two alternative sequences are found in a population. “Past studies that compared the entire modern human genome with the Neanderthal or the chimpanzee genomes have focused on changes that are fixed or nearly fixed in modern humans. This has led to them identifying sites where, for example, all Neanderthals had Adenine (one of the four nucleotides that with guanine, cytosine and thymine form the DNA) and nearly all modern humans (say, 98%) have Guanine. In this study, we searched for differences on locations where, by definition, not all modern humans share the same nucleotide, namely on polymorphic sites, where for example, 70% of the modern human population has Adenine and 30% Cytosine,” adds Theofanopoulou.
The researchers identified five sites in the oxytocin and vasotocin receptors where modern humans are unique in one of their two (or more) variants compared to archaic humans and non-human primates, and which are at the same time found in more than 70% of the modern human population. Next, they conducted functional and frequency analyses to establish whether the variants are relevant. They performed a range of analyses on the five sites and found that some of the variants are highly functional, indicating that they have an effect on the molecular function of the proteins activated by these genes.