Fibrotic diseases is a cover term coined by our laboratory to address complications of the excessive scarring of fibrous tissue. They occur when fibroblasts – a critical component of the structural tissue of the body – proliferate and include, but are not limited to lung fibrosis, kidney and liver fibrosis, scleroderma, wound healing and surgical adhesions. Despite fibrotic diseases being life-threatening-- the mortality rate of some are higher than that of cancer-- current treatments are ineffective and/or entirely nonexistent.
Our mission is to identify new targets for treatment through uncovering the underlying mechanisms of fibrosis. We seek to understand how fibroblasts crosstalk with one another, with the immune system, and with epithelial and mesenchymal cells. By utilizing mass cytometry, gene expression and chromatin studies of patient-derived primary tissues in combination with in vivo modeling of fibrotic disease in mice, we gain insight into the pathophysiology of fibrotic diseases. We employ immunotherapy combined with small molecules in order to manipulate signaling pathways at the transcriptional level to disrupt pro-fibrotic cell function and fate. The transcriptional networks we study play key roles in fibrotic disease, metabolism, bone physiology, cancer, and immunology. Understanding them will provide the critical foundation to translate our findings into immunotherapies and clinical practice.
Idiopathic lung fibrosis is a debilitating disease with a dismal prognosis and which is currently is incurable. The disease is caused by progressive scarring in the lungs, making it difficult to breathe for patients who become dependent on oxygen to live. Now a team of researchers led by assistant professor of pathology Gerlinde Wernig, MD, at the Stanford Institute for Stem Cell Biology and Regenerative Medicine has shown that scar tissue cells called fibroblasts are able to proliferate by avoiding immune surveillance, and that a cure may lie in reactivating that immune function. Their work was published online in the journal Nature Communications on June 3, 2020.
We identified a pathway that, when mutated, drives fibrosis in many organs of the body. The pathway underlies what have been considered somewhat disparate conditions, including scleroderma, idiopathic pulmonary fibrosis, liver cirrhosis, kidney fibrosis and more. These diseases are often incurable and life-threatening.
Coverage in Scleroderma News of our work to identify a key element that is responsible for fibrosis of many incurable and life-threatening diseases, such as scleroderma. The finding helps to develop new specific and efficient treatments to reverse tissue fibrosis processes
WorldHealth.net covered our work to determine that it is possible to reverse fibrosis. We found that fibrotic diseases that occur in humans are united with a common signaling pathway. The research team determined that the antibody anti-CD47 reverses fibrosis in mice. Anti-CD47 is currently being tested as an anti cancer agent.
• Elected to Member of the Institute for Regenerative Medicine and Stem Cell Research at Stanford
• Ludwig Investigator award
• Boehringer-Ingelheim Idiopathic pulmonary fibrosis Investigator award
• K08 award, National Institute of Health, NHLBI
• Scleroderma research foundation, Young investigator award
• Desmoid tumor research foundation, Young investigator award
Just three years after discovering a genetic mutation that causes a trio of leukemias, we helped move a new leukemia drug into clinical trials. As part of the Howard Hughes Medical Institute (HHMI), our drug which is based on strong preclinical data has been approved by the FDA for human trials. Our tests in mince populations showed that the drug eliminates clinical manifestation of the leukemias without significant toxicity.
Exploring the fundamental mechanism by which a cell-surface receptor transmits its signal, our team of Ludwig researchers and our colleagues has established proof of concept for an entirely new approach to drug design. Wereport that a class of synthetic molecules known as diabodies can, from outside the cell, latch onto a target receptor and manipulate it in such a manner as to induce distinct and varying effects within cells and tissues. In lab experiments how this might work, using a diabody to stall the growth of cancer cells isolated from patients with myeloproliferative neoplasms.
Gerlinde is a pathologist by trade whose research centers around the mechanisms of fibrosis and new treatments. She enjoys staying active by hiking in the mountains and sprinting between clinic and lab. She finds optimizing complex lab protocols as gratifying as perfecting the recipes in her side-gig as an undercover chef.
Cristabelle De Souza is a recent addition to our lab from UC Davis Medical Center. Armed with a Ph.D. in Cancer Biology she joins our team as a researcher steering our investigations into fibrotic research further. A classic type A personality, she constantly likes to be on the move. In addition to science and medicine, she is trained in latin american dancing and plays the guitar which keeps research frustrations at bay. She also likes to live life on the edge and takes part in adventure sports. Cristabelle says she is a terrible cook and is always looking up seminars that provide free lunch!
Qiwen Deng loves science and research, she is interested in studying innate immunity and fibrosis in endstage kidney disease in the setting of diabetic nephropathy. When she is not working in the lab (which is almost never) she enjoys traveling, reading, fine art and good food and playing pool with friends.
Marjia is working on solving the challenges around Scleroderma Interstitial Lung disease. She is developing next generation of organoid platforms incorporating the immune response suitable for screening of immune therapy candidates.
Elsa Balfe is a recent Cellular Molecular BiologyBachelor of Science graduate from Cal Poly Humboldt and is currently a CIRM Bridges intern. With a passion for understanding, preventing, and alleviating pathological states, she aspires to gain a Ph.D. in nutrigenomics, nutritional biochemistry, or a related discipline. To remain balanced, her personal interests include exploring in the forest, indulging in new recipes, tending to plants, reading, and spending quality time with family and friends.
Ariana Motaghian is a highschool student at Los Altos High School and research intern in the lab. Ariana's interests are in cancer biology and fibrotic diseases, as well as how to utilize CRISPR to accelerate research of diseases. Outside the lab, Ariana enjoys hiking, cooking, and spending time with her family.
My research interest is in understanding the mechanisms of reactive oxygen species (ROS) in CD8 T cells. Therefore, during my PhD research, I built a ROS panel for CyTOF and analyzed the regulatory mechanism of CD8 T cells in diseases and cancers. Besides research, I love traveling and am working on completing my travel bucket list!
Paul Wadsworth loves science, nature, and sci fi novels! He is currentlya resident in pathology with interests in molecular genetics andhematopathology. He completed his PhD in Biochemistry working on a project inhigh-throughput screening for both drug discovery and cell signaling pathwaysinvolved in neuroinflammation. He is interested in elucidating the cellularmechanisms of cGVHD pathogenesis with the intent of developing new avenues forimmune therapies. If he’s not reading assay and instrument manuals in the lab,then you can find him hiking at the state parks or reading science fiction!
Clarissa Yiu has a passion for scientific research and is currently a life science major at UC Davis. During Summer 2022, she worked for 3 months full term as a summer intern in the lab on various projects involving the don't eat me signal CD47 and metabolic syndrome. Already during her highschool years she shared her love of science by mentoring middle school girls on science projects. She hopes to be a Ph.D./M.D. scientist to help patients in the future. She enjoys reading, hiking, biking, roller-skating, traveling, eating good food, and experimenting with cooking recipes in her free time.
Atif Saleem has been training in Hematopathology and Dermatopathology at Stanford : this mélange of interests makes him enthusiastic and grateful to be in the Wernig lab. He is interested in patho mechanisms of GVHD driving fibrosis, in addition interested in effects of viruses on the immune repertoire and disease. Outside the lab, you can find him getting injured snowboarding or probably jet-lagged given his interest of global health.
Megan King was our CIRM student who moved onto now in medical school UC San Diego.
Prospective major in Chemistry, biological chemistry track
Prospective major in Biology
Majored in Bioengineering now applying to medical school.
After she had graduated from college at Stanford, Camille was working on mechanism of fibrosis in the lab. She decided to pursue a career as a physician-scientist and is now an MD and Phd candidate at Mount Sinai Medical School, NY.
Having once dreamt of becoming a pilot and a soccer player, Tristan instead found his calling in medicine. He is studying the effects of transcriptional programs on osteopenia and dermal fibrosis. In his free time (he has none), he enjoys musicals and going to the opera, and flying a small airplane. He manages to sneak in tennis and gym sessions in between incubation periods, and his role model is Mark Wahlberg from Pain & Gain. He moved on to Residency in Pathology.
Lu has been leading the discovery on how immune modulatory mechanisms play a crucial role in IPF lung fibrosis. This research is the first in its kind demonstrating that immunotherapy could work against fibrosis and lung fibrosis. She normally has a lot of different projects on her plate, but she tackles them without hesitation. Also found on her plate are the aromatic home-cooked meals she brings for lunch everyday that make other members hungry before their own lunch break. Her source of energy is hiking every other week with her family.
Yong-hun has majored from computer science with a focus in biocomputation. During his undergraduate years he helped with studies to develop immune therapies as a treatment for lung fibrosis in our lab. Yong-hun recently graduated and received his master in computer science from Stanford. Yong-hun was accepted into Mayo Clinic Medical School and will start his medical training in fall 2020.
A cactus hailing from the dusty town of Tucson, Alexa is a summer student majoring in Molecular and Cellular Biology. Despite her nitrile allergy, she enjoys being in lab where she aims to better understand transcriptional factors of bone development. When she is not in the imaging room, Alexa is taking pictures of her food and embarrassing the people with her.
Wound healing – collaboration with Dr. Longaker lab
Chronic Graft-versus Host Disease – collaboration with Dr. Shizuru lab
Lung fibrosis – collaboration with Dr. Desai lab
Scleroderma – Drs. Howard Chang lab, Lori Chung
Eye: Hyperthyroidism, cGVHD, IgG4 disease – collaboration with Dr. Wu lab
Fibrotic tumors/Desmoids - collaboration with Drs. van de Rijn lab/Kumar
Tumor stroma – collaboration with Dr. Plevritis lab
Metabolism and immunity – collaboration with Dr. Weissman lab
Small molecules with antifibrotic properties – collaboration with Dr. Malhotra lab
cJUN drives expansion of bone stem and progenitors – collaboration with Dr. Charles Chan lab