The Mostoslavsky Lab

Mission Statement

The Mostoslavsky Lab is a basic science laboratory in the Section of Gastroenterology in the Department of Medicine at Boston University, affiliated with the Boston University Center for Regenerative Medicine (CReM). Our goal is to study human biology in normal and disease states, through the use of stem cells in general and pluripotent stem cells in particular, with major focuses on gastrointestinal tract, neurodegeneration caused by prion diseases and immunity/inflammation. We believe that by discovering the mechanisms involved in stem cell self-renewal and differentiation we will be able to manipulate stem cell fate and use it as the basis for the correction of several diseases. Taking advantage of our long history of genetic manipulation, we are using gene editing techniques (such as CRISPR based editing) to generate a variety of reporter lines as well as isogenic mutant vs corrected iPSC lines for the study of lineage specification as well as disease modeling.

The Principal Investigator

Gustavo Mostoslavsky, MD PhD

Dr. Mostoslavsky received his MD from the University of Tucuman in Argentina and his PhD from the Hebrew University in Jerusalem, Israel. His longstanding interest in basic science and regenerative medicine brought him to Harvard Medical School to pursue postdoctoral studies with stem cells and gene therapy. In 2008 Dr. Mostoslavsky opened his own lab at Boston University. He is currently Professor of Medicine in the Section of Gastroenterology in the Department of Medicine at Boston University School of Medicine. His main research interests are stem cells, disease modeling, regenerative medicine, gene correction and lentiviral vectors as tools for gene transfer. Dr. Mostoslavsky is a founder and Co-Director of the BU Center for Regenerative Medicine (CReM).

Areas of Research

iPS cells

Our lab has a major interest in the study of induced Pluripotent Stem cells or iPS cells and the development of tools for their generation and characterization. Pioneering work by the laboratory of Dr. Yamanaka showed that fibroblasts transduced with retroviral vectors expressing four transcription factors, Oct4, Klf4, Sox2 and cMyc can be reprogrammed to become pluripotent stem cells that appear almost indistinguishable from ESC. In contrast to ESC, iPS cells are genetically identical to the individual from whom they are derived, raising the prospect of utilizing iPS cells for autologous cell based therapies without risk of rejection. We have previously developed a single lentiviral vector expressing a stem cell cassette, named STEMCCA, capable of generating iPS cells from post-natal fibroblasts and peripheral blood with very high efficiency that became the industry standard. We have also modified it to make it excisable and have used it to generate mouse and human iPS cells free of exogenous transgenes. For the last several years we have used iPS cells for disease modeling and study their potential for regenerative medicine.

iPS Cell Modeling of Intestinal Differentiation

One major focus of the lab is the utilization of iPS Cells for the study of intestinal differentiation with a particular interest in infectious diseases as well as Colorectal Carcinoma (CRC). For this purpose we have generated iPSC from individuals suffering from FAP and Lynch Syndrome, the two most highly penetrant hereditary forms of CRC. We have established in the lab robust differentiation protocols for the induction of intestinal specification of these disease-specific iPSC. By studying the earlier events associated with intestinal differentiation comparing the normal and mutant cells we aim at discovering the basic mechanisms involved in tumor development in the gastrointestinal tract. We are also very interested in studying viral infections of the gut. For this purpose we have used our HIO differentiation protocol to study the effect of SARS-CoV-2 in affecting the intestinal epithelium and we are now expanding these studies to compare Ebola virus vs Marburg virus infection of the gut.

FAP-specific iPSC-derived intestinal organoids

iPS Cell Modeling of Hepatic Differentiation

Several projects in the lab utilizes the liver differentiated progeny of iPSC to study genetic and infectious diseases affecting the liver. We have an established collaboration with the Mühlberger lab at the BU NEIDL to study Ebola virus entry and replication utilizing human iPSC-derived hepatocytes. By accessing primary human target cells we hope to establish a new paradigm in the use of iPSC-derived cells for infectious diseases.

Ebola viral inclusions in human iPSC-derived hepatocytes

iPS Cell Modeling of Immune / Inflammatory Cell Differentiation

Our long standing interest in the immune system now focuses in the utilization of iPSC-derived immune cells, including myeloid dendritic cells (mDCs), microglia, T cells and others as the basis to study several inflammatory and infectious diseases such as filovirus infection and HIV. In collaboration with the Gummuluru and Henderson labs we are utilizing iPSC-derived microglia cells to study the role of microglia in HIV latency in the neural system, as well as the role of opiod addiction in affecting HIV infection. Another project in the lab focuses on the generation of T/NK cells and their potential use as modulators of immune tolerance and immunotherapy. We are combining novel engineered lines, notch signaling stimulation and gene editing to explore a way to direct the differentiation of iPSC into hematopoietic progenitors and into a T/NK cell lineage.

CJD-specific iPSC-derived motor neurons express high levels of PrP protein

iPS Cell Modeling of Neurodegeneration

We have established the largest iPSC library of E200K mutant cells from individuals with Creutzfeldt Jakob Disease. We are utilizing their differentiated motor neurons and astocytes to study expression of normal vs mutant PrP and the mechanisms behind Prion mediated neural toxicity. We have also created syngeneic CRISPR corrected lines and we are establishing cerebral organoids from normal and mutant cells to study the role of abnormal prion protein in these organoids.

Lab Members

Aldana Gojanovich, PhD | Postdoctoral Research Fellow

Aldana was born in a small town called Verónica in the province of Buenos Aires, Argentina. Aldana holds a Biotechnology and Molecular Biology degree from the University of La Plata (UNLP) and a Ph.D. in Biological Sciences from the University of Buenos Aires (UBA). After spending three years in Mendoza (becoming an expert in Malbec) she joined the Mostoslavsky Lab to develop an iPSCs-based model of neurodegenerative diseases using patient-specific iPSC with mutations causing Creutzfeldt-Jakob Disease. Outside the lab Aldana enjoys walking around Boston, good music, good food and watching TV series and movies.

Charlie Kerr, PhD | Postdoctoral Research Fellow

Charlie grew up in Pittsburgh, Pennsylvania but have lived in South Carolina for several years. He received his PhD from the Medical University of South Carolina where he studied hiPSC-derived cardiovascular organoids. Now, he is interested in immunology and am enthusiastic to begin exploring immune cell applications in regenerative medicine. In his spare time, he is outgoing and enjoy most outdoor activities. Lately, he has been playing a lot of tennis and backpacking/hiking. Some of his other hobbies include trying out new recipes and binging TV shows. “I am happy to become a member of the CReM!

Elizabeth Yvonne (Liz) Flores | PhD Student

Liz is a PhD student in the Mostoslavsky and Mühlberger labs at Boston University. She is originally from California, but has spent most of her life on the East Coast. She graduated with a BS in Biology and an MS in Molecular Biology from Montclair State University. She is broadly interested in the molecular mechanisms underlying infectious diseases and is currently modeling filovirus infections in iPSC-derived human intestinal organoids. Aside from scientific research, Liz loves attending art galleries, playing the piano, traveling and film.

Julian Amirault | PhD Student

Julian is a PhD student in the Mostoslavsky lab studying T cell differentiation and the molecular mechanisms governing CD8 vs CD4 lineage specification. Building on our previous studies of the role of Notch signaling in early definitive hematopoietic specification, Julian is exploring the signaling cues that modulate the generation of T cell lymphocytes from human iPSC.

Anna Maria Didier | Undergraduate Student

Anna Maria Didier is an incoming junior at Boston University studying Human Physiology. She is originally from Brazil but grew up in Northern NJ. Since coming to BU, she has fallen in love with Boston and tries to explore something new with her roommates each weekend. In her free time she loves baking, reading, and binging any new Netflix original that everyone else is watching.

Victor Schingo | Undergraduate Student

Victor is currently a Biochemistry major/molecular biology/pre-med student at Boston University. He currently has the tough task of utilizing iPSC containing inducible forms of oncogenes relevant to Colorectal cancer to study the initiation of tumorigenes in the GI tract using iPSC-derived intestinal organoids.

Andrew D'Amico | Research Technician

Andrew is a research technician in the Mostoslavsky lab from Wayland, Massachusetts. He recently graduated from Tufts University with a BS in Biochemistry and plans to apply to medical school. Outside the lab Andrew enjoys playing and watching soccer, skiing, and spending time with family.

MengWei Yang | Lab Manager

MengWei graduated from University of Massachusetts Amherst with a bachelor’s degree in Biology and Chinese. MengWei is the current lab manger for the Mostoslavsky lab. He was born in Fuzhou, China but immigrated to the United States at the age of 7. In his free time he loves being outdoors and fishing. One fun fact about him is that he plays the clarinet.