New Publication in Molecular & Cellular Proteomics from the Zaia Lab

The Zaia Lab, in collaboration with Prof. Joanna Phillips of the Dept. of Nerological Surgery at the University of California San Francisco, has a new publication out in Molecular & Cellular Proteomics, "In-depth matrisome and glycoproteomic analysis of human brain glioblastoma versus control tissue."

Glioblastoma (GBM) is the most common and malignant primary brain tumor. The extracellular matrix (ECM), also known as the matrisome, helps determine glioma invasion, adhesion, and growth. Little attention, however, has been paid to glycosylation of the ECM components that constitute the majority of glycosylated protein mass and presumed biological properties. To acquire a comprehensive understanding of the biological functions of the matrisome and its components, including proteoglycans and glycosaminoglycans (GAGs), in GBM tumorigenesis, and to identify potential biomarker candidates, we studied the alterations of GAGs, including heparan sulfate (HS) and chondroitin sulfate (CS), the core proteins of proteoglycans, and other glycosylated matrisomal proteins in GBM subtypes vs. control human brain tissue samples. We scrutinized the proteomics data to acquire in-depth site-specific glycoproteomic profiles of the GBM subtypes that will assist in identifying specific glycosylation changes in GBM. We observed an increase in CS 6-O sulfation and a decrease in HS 6-O sulfation, accompanied by an increase in unsulfated CS and HS disaccharides in GBM vs. control samples. Several core matrisome proteins, including proteoglycans (decorin, biglycan, agrin, prolargin, glypican-1, CSPG4), tenascin, fibronectin, hyaluronan link protein 1 and 2, laminins, and collagens, were differentially regulated in GBM vs. controls.

Interestingly, a higher degree of collagen hydroxyprolination was also observed for GBM vs. controls. Further, two proteoglycans, CSPG4, and agrin were significantly lower, about 6–fold for IDH-mutant, compared to the WT GBM samples. Differential regulation of O-glycopeptides for proteoglycans, including brevican, neurocan, and versican, was observed for GBM subtypes vs. controls. Moreover, an increase in levels of glycosyltransferase and glycosidase enzymes was observed for GBM when compared to control samples. We also report distinct protein, peptide, and glycopeptide features for GBM subtypes comparisons. Taken together, our study informs understanding of the alterations to key matrisomal molecules that occur during GBM development.

Corresponding author- Prof. Joseph Zaia, Dept. of Biochemistry, Center for Biomedical Mass Spectrometry, Boston University.

Collaborator- Prof. Joanna Phillips, Dept. of Neurological Surgery, Brain Tumor Center, Helen Diller Family Cancer Research Center, University of California San Francisco, Division of Neuropathology, Department of Pathology, University of California San Francisco.

Remi Janicot awarded American Heart Association fellowship

Remi Janicot in the Garcia-Marcos laboratory was awarded an American Heart Association (AHA) predoctoral fellowship for his project "Optical biosensor platforms for the direct interrogation of GPCR signaling in cardiovascular cells”

The goal of this project is to create new experimental tools that can transform how GPCRs are studied. The main benefit over current methods is that these tools can be easily used in cell models that are relevant to study heart or lung disease, which has been an important limitation in the field. These new experimental possibilities would open new doors for the entire cardiovascular research community. The tools designed in this project will allow to study GPCRs with fidelity and precision. This would pave the way to develop new drugs to treat life-threatening cardiac disorders.

Congratulations Remi!


Kristen Segars Receives F30 Grant for Work with Diabetic Corneal Epithelia

Congratulations to Kristen Segars, an MD/PhD candidate in Dr. Trinkaus-Randall’s lab, for her receipt of an F30 grant for her work, “Delayed wound healing in diabetic corneal epithelia: reduction in protein response after injury and uncoordinated cell-cell communication."

Non-healing corneal injuries affect up to 70% of patients with type 2 diabetes, representing a significant cause of vision loss in this population. Although there are treatments available to improve the symptoms of poorly-healing corneal wounds, the only permanent solution is a corneal transplant, a procedure not readily available worldwide. By examining changes in various proteins involved in the wound healing response at the cellular level, Segars hopes to understand why the corneas of diabetic patients fail to heal effectively.

When an otherwise healthy cornea is injured, cells next to the wound experience a number of changes necessary for coordinated migration and wound closure. One change involves the activation of the purinergic receptor, P2X7, found on the cell surface. When active, P2X7 generates a specific pattern of calcium signaling events that travel from cell to cell through activation of the ion channel Pannexin-1. These propagated signaling events represent cell-cell communication, and ultimately lead to re-arrangement of cytoskeletal proteins and coordinated wound closure. Previous studies have identified aberrant localization and activation of P2X7 in pre-type 2 diabetic models. We have preliminary evidence that the signaling profile of wounded diabetic cells lacks the characteristic P2X7 signaling response. This was confirmed using specific agonists to P2X7, and observing a greatly diminished response in diabetic cells. The goal of this proposal is to uncover how the cell-cell communication events in the P2X7 signaling cascade are regulated, how this regulation is thrown off in diabetic systems, and how this change in regulation affects actin bundling and ultimately cell motility.

Segar's preliminary data has identified a set of cells that she speculates are controllers or leader cells, as they initiate communication events in neighboring cells, and propagated signaling events are greatly reduced in their absence. Aim 1 will use a machine learning approach to investigate the presence of these leader cells in both diabetic cell culture and corneal models. Aim 1 will also address the role of Pannexin-1 in the generation of a unique leader cell signaling profile. Furthermore, the downstream impact of P2X7/Pannexin-1 signaling will be assessed by using 3D electron microscopy to study actin arrangement in wounded diabetic and control corneas. In Aim 2, the localization of P2X7 and Pannexin-1 protein and mRNA within the cells of corneal samples will be examined. This will yield data regarding both general trends in expression between diabetic and control groups, and differences in expression within a single sample that may explain the functional difference between leader cells and the rest of the epithelial sheet. In addition, Aim 2 will address whether the co-localization of P2X7 and Pannexin-1 proteins (before and after a wound) is necessary for wound repair. Together these Aims will produce significant advances in our understanding of the regulation of the P2X7/Pannexin-1 signaling cascade, alterations at the mRNA, protein, and functional level of this cascade in diabetes, and downstream effects of these aberrations on the actin cytoskeleton.

Obesity-induced senescent macrophages and fibrosis

As organisms grow, older cells can undergo a phenomenon called senescence. This process defines a cell state where cells permanently stop dividing but do not die. Senescent cells secrete toxic pro-inflammatory factors contributing to the development of many diseases.

BUSM researchers have shown that obesity in experimental models led to senescence of macrophages, an immune cell subtype within fat or adipose tissue published online in the journal Life Science Alliance. Obesity-induced senescent macrophages activate a fibrotic transcriptional program in adipocyte progenitors by Nabil Rabhi, Kathleen Desevin, Anna C Belkina, Andrew Tilston-Lunel, Xaralabos Varelas, Matthew D Layne, Stephen R Farmer

According to the researchers, the fact that macrophages can become senescent is an unexpected finding. Many of the macrophages within obese tissue were senescent and those senescent cells may be a significant driver of fat tissue fibrosis. These findings suggest that obesity accelerates cellular or biological immune aging in fat.

“In healthy individuals, those cells contribute to cleaning the tissue from dead adipocytes (cells specialized for the storage of fat) and help in the cellular turnover. We demonstrated that macrophages lost this capacity when they become senescent,” explained first and co-corresponding author Nabil Rabhi, PhD, an instructor of biochemistry at BUSM.

The researchers also found that senescent macrophages secrete a variety of factors, one of which is a molecule called osteopontin which they found is responsible for adipose tissue fibrosis. “Our finding suggests that macrophages ages faster in obese animals. This accelerated senescence may contribute to the pathological thickness or fibrosis of fat tissue observed in obese individuals with type 2 diabetes,” said Rabhi.

The researchers believe understanding new regulatory pathways that control adipose tissue responses to obesity may help identify new targets for obesity treatment. “Our finding indicates that targeting the senescent macrophages population or using osteopontin inhibition may represent a promising approach for obesity treatment and its adverse complication including type 2 diabetes,” added Rabhi.

Dmitry Kretov selected for early career development award

February 14th, 2022in Departmental News, Research News

Congratulations to Dmitry Kretov for being selected for a Department of Biochemistry Early Career Development Award. Dmitry is an Instructor working in the Cifuentes laboratory on a project entitled: “Development of an integrative approach to reveal the specificity of RNA-binding proteins and their effect on mRNA stability and translation in vivo”. This award is $21,000 for 1 year.

SARS-CoV-2 Access into Cells

February 2nd, 2022in Departmental News, Research News

The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human cells is an essential step for virus transmission and development of COVID 19. Although the lung epithelial cells are its initial target, SARS-CoV-2 also can infect endothelial cells. Endothelial cells are the major constituents of the vascular system and cardiovascular complication is a hallmark of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2. However, the possible involvement of other cellular components in the viral entry is not fully understood.

A team of BUSM researchers has identified extracellular vimentin as an attachment factor that facilitates SARS-CoV-2 entry into human cells. Vimentin is a structural protein that is widely expressed in the cells of mesenchymal origin such as endothelial cells and a potential novel target against SARS-CoV-2, which could block the infection of the SARS-CoV-2.

“Severe endothelial injury, vascular thrombosis, and obstruction of alveolar capillaries (tiny air sacs scattered throughout the lungs) are common features of severe COVID-19. Identification of vimentin as a host attachment factor for SARS-CoV-2 can provide new insight into the mechanism of SARS-CoV-2 infection of the vascular system and can lead to the development of novel treatment strategies,” said co-corresponding author Nader Rahimi, PhD, associate professor of pathology & laboratory medicine.

The researchers used liquid chromatography–tandem mass spectrometry (LC-MS/MS) and identified vimentin as a protein that binds to the SARS-CoV-2 spike (S) protein and facilitates SARS-CoV-2 infection. They also found that depletion of vimentin significantly reduces SARS-CoV-2 infection of human endothelial cells. In contrast, over-expression of vimentin with ACE2 significantly increased the infection rate. “More importantly, we saw that the CR3022 antibody inhibited the binding of vimentin with CoV-2-S-protein, and neutralized SARS-CoV-2 entry into human cells,” explained Rahimi.

“The course of infection with SARS-Cov-2 is dependent on multiple factors that affect the attachment and entry of the virus into host cells, so casting a wide net and using multiple approaches to define and validate the critical components is an important strategy that can lead to the identification of protective or therapeutic targets. We show here that, in the vascular system, vimentin plays a key role in attachment of the virus to its best-known receptor, ACE2; we determined in an earlier paper in the journal ACS Central Science that CD209 and CD209L are alternative receptors that may expedite infection of tissues where ACE2 has low abundance,” said co-corresponding author Catherine E. Costello, PhD, William Fairfield Warren Distinguished Professor, Biochemistry and director of the Center for Biomedical Mass Spectrometry at BUSM.

Other collaborators from BUSM include Elke Mühlberger, PhD, and Vipul Chitalia, MD, PhD.

Story from BUSM:

These findings appear online in the Proceedings of the National Academy of Sciences.

Mikel Garcia-Marcos receives John Abel Award from ASPET

January 13th, 2022in Departmental News, MGM lab, Research News

Congratulations to Dr. Mikel Garcia-Marcos for receiving the 2022 American Society for Pharmacology and Experimental Therapeutics (ASPET) John J. Abel Award in Pharmacology. The Abel Award is named after the founder of ASPET. It was established in 1946 to stimulate fundamental research in pharmacology and experimental therapeutics by young investigators.

The award will be presented at the ASPET Business Meeting and Awards Presentation during the ASPET Annual Meeting at Experimental Biology 2022 on Saturday, April 2 at 4:30 pm in Philadelphia. Additionally, Dr. Garcia-Marcos will deliver the Abel Award Lecture titled The Secret Life of G Proteins to open the 2022 annual meeting on Saturday, April 2 at 10:00 am in Philadelphia.

New Publication by Jarrod Moore in International Journal of Molecular Sciences

A first publication by Jarrod Moore, an MD, PhD candidate at Boston University School of Medicine and student of the Center for Network Systems Biology, in the International Journal of Molecular Sciences, looking at hypertrophic cardiomyopathy, "Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy."

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease thought to be principally caused by mutations in sarcomeric proteins. Despite extensive genetic analysis, there are no comprehensive molecular frameworks for how single mutations in contractile proteins result in the diverse assortment of cellular, phenotypic, and pathobiological cascades seen in HCM. Molecular profiling and system biology approaches are powerful tools for elucidating, quantifying, and interpreting dynamic signaling pathways and differential macromolecule expression profiles for a wide range of sample types, including cardiomyopathy. Cutting-edge approaches combine high-performance analytical instrumentation (e.g., mass spectrometry) with computational methods (e.g., bioinformatics) to study the comparative activity of biochemical pathways based on relative abundances of functionally linked proteins of interest. Cardiac research is poised to benefit enormously from the application of this toolkit to cardiac tissue models, which recapitulate key aspects of pathogenesis. In this review, we evaluate state-of-the-art mass-spectrometry-based proteomic and phosphoproteomic technologies and their application to in vitro and ex vivo models of HCM for global mapping of macromolecular alterations driving disease progression, emphasizing their potential for defining the components of basic biological systems, the fundamental mechanistic basis of HCM pathogenesis, and treating the ensuing varied clinical outcomes seen among affected patient cohorts. 

Jarrod Moore is in his third doctoral year, which includes combined mass-spectrometry-based proteomics and tissue engineering training. His work is generously supported through the Kilachand Fellowship from the Multicellular Design Program at Boston University and the MD/PhD program at Boston University School of Medicine.

The article can be accessed here:


Faculty Position Available

December 1st, 2021in Departmental News, Research News

The Boston University Departments of Biology (College of Arts & Sciences) and Biochemistry (School of Medicine) invite applications for a tenure-track Assistant Professor position in Systems Biology starting in Fall 2022. We seek to recruit a colleague who uses high-throughput experimental and systems-level approaches to elucidate complex and dynamic biological processes, such as cell signaling, development in model organisms, epigenetic regulation, metabolism, nervous system function, protein homeostasis/trafficking, or transcriptional control. This search builds on recent faculty growth in systems biology and establishment of the Center for Network Systems Biology and seeks to generate new research synergies. Responsibilities include growing a vibrant research program with extramural funding, teaching graduate and/or undergraduate courses, and mentoring graduate students in research, with opportunities to participate in several interdisciplinary graduate programs. The successful candidate will be jointly appointed in Biology and Biochemistry and will contribute to a strong and growing interdisciplinary systems biology research community at Boston University that also benefits from close affiliations with engineering initiatives (including Photonics and Biological Design), and with clinical/translational efforts at the medical school. Boston University expects excellence in teaching and in research, and is committed to building a culturally, racially, and ethnically diverse scholarly community. The successful candidate will be offered newly renovated laboratory facilities as well as a competitive salary and generous start-up package.

Review of applications will begin 15 December 2021. Please use AcademicJobsOnline to submit a cover letter, curriculum vitae, statements of research, teaching interests and diversity, and three representative reprints, and arrange for three letters of reference to be submitted through the same website. In the diversity statement, applicants should provide evidence of a commitment to fostering diversity, equity, inclusive excellence, and evidence of participation in the creation of inclusive environments in their department/workplace. Inquiries can be addressed to Andrew Emili (, Chair, Systems Biology Search Committee. Please visit the following websites for information about the Biology Department and the Department of Biochemistry.

In a continuing effort to enrich its academic environment and provide equal educational and employment opportunities, the university actively encourages applications from members of all groups underrepresented in higher education. Boston University is an AAU institution with a rich tradition of inclusion and social justice. We are proud to be the first American university to award a Ph.D. to a woman, and we continue that tradition of educating a diverse and talented student body. We are an equal opportunity employer and all qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability status, protected veteran status, or any other characteristic protected by law. We are a VEVRAA Federal Contractor.