Maia Shoham

All Publications

• SIRPα controls CD47-dependent platelet clearance in mice and humans. bioRxiv : the preprint server for biology Shoham, M., Yiu, Y. Y., Hansen, P. S., Subramaniam, A., Broberg, M., Gars, E., Raveh, T., Weissman, I. L., Sinnott-Armstrong, N., Krishnan, A., Ollila, H. M., Tal, M. C. 2023

  Abstract

  Over the last decade, more data has revealed that increased surface expression of the "don't eat me" CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 is critical in regulating cell homeostasis and clearance, as binding of CD47 to the inhibitory receptor SIRPα can prevent phagocytosis and macrophage-mediated cell clearance. The purpose of this study was to examine the role of the CD47-SIRPα signal in platelet homeostasis and clearance. Therapeutic reagents targeting the CD47-SIRPα axis are very promising for treatment of hematologic malignancies and solid tumors, but lead to transient anemia or thrombocytopenia in a subset of patients. We found that platelet homeostatic clearance is regulated through the CD47-SIRPα axis and that therapeutic blockade to disrupt this interaction in mice and in humans has a significant impact on platelet levels. Furthermore, we identified genetic variations at the SIRPA locus that impact platelet levels in humans such that higher SIRPA gene expression is associated with higher platelet levels. SIRPA expression at either end of the normal range may affect clinical outcomes of treatment with anti-CD47 therapy.

  View details for DOI 10.1101/2023.12.09.570874

  View details for PubMedID 38106070

  View details for PubMedCentralID PMC10723388

• Considerations for secondary vaginoplasty TRANSLATIONAL ANDROLOGY AND UROLOGY Shoham, M., Pang, J., Satterwhite, T. 2022: 1480-1483

  View details for DOI 10.21037/tau-22-660

  View details for Web of Science ID 000890843000001

  View details for PubMedID 36507476

  View details for PubMedCentralID PMC9732695

• The environmental impact of surgery: A systematic review. Surgery Shoham, M. A., Baker, N. M., Peterson, M. E., Fox, P. 2022

  Abstract

  BACKGROUND: Climate change is a significant public health threat. Health care comprises 10% of greenhouse gas emissions in the United States, where surgery is especially resource intensive. We did a systematic review to assess and summarize the published evidence of the environmental impact of surgery.METHODS: We searched Medline, Embase, Web of Science, and GreenFILE databases for publications that report any environmental impact measure by all surgical subspecialties, including anesthesia. Inclusion criteria were published in English, original research, and passed peer review. Because data were heterogeneous and the aim was broad, we conducted a qualitative summary of data. Where possible, we compare impact measures.RESULTS: In the study, 167 articles were identified by our search strategy and reviewed, of which 55 studies met criteria. Eight were about anesthesia, 27 about operating room waste, and 6 were life cycle assessments. Other topics include carbon footprint and greenhouse gas emissions. Nine papers fell into 2 or more categories. Overall, the operating room is a significant source of emissions and waste. Using anesthetic gases with low global warming potential reduces operating room emissions without compromising patient safety. Operating room waste is often disposed of improperly, often due to convenience or knowledge gaps. There are environmental benefits to replacing disposable materials with reusable equivalents, and to proper recycling. Surgeons can help implement these changes at their institution.CONCLUSION: Although there is a clear need to lower the carbon footprint of surgery, the quality of research with which to inform protocol changes is deficient overall. Our attempt to quantify surgery's carbon footprint yielded heterogeneous data and few standardized, actionable recommendations. However, this data serves as a starting point for important future initiatives to decrease the environmental impact of surgery.

  View details for DOI 10.1016/j.surg.2022.04.010

  View details for PubMedID 35788282

• The Environmental Impact of Surgery Shoham, M., Baker, N., Peterson, M., Fox, P. ELSEVIER SCIENCE INC. 2021: S133

  View details for Web of Science ID 000718303100242

• CD47 blockade reduces the pathologic features of experimental cerebral malaria and promotes survival of hosts with Plasmodium infection PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Dulgeroff, L., Oakley, M. S., Tal, M. C., Yiu, Y., He, J. Q., Shoham, M., Majam, V., Okoth, W. A., Malla, P., Kumar, S., Weissman, I. L. 2021; 118 (11)

  View details for DOI 10.1073/pnas.1907653118

  View details for Web of Science ID 000629635100001

• CD47 blockade reduces the pathologic features of experimental cerebral malaria and promotes survival of hosts with Plasmodium infection. Proceedings of the National Academy of Sciences of the United States of America Torrez Dulgeroff, L. B., Oakley, M. S., Tal, M. C., Yiu, Y. Y., He, J. Q., Shoham, M., Majam, V., Okoth, W. A., Malla, P., Kumar, S., Weissman, I. L. 2021; 118 (11)

  Abstract

  CD47 is an antiphagocytic "don't eat me" signal that inhibits programmed cell removal of self. As red blood cells (RBCs) age they lose CD47 expression and become susceptible to programmed cell removal by macrophages. CD47-/- mice infected with Plasmodium yoelii, which exhibits an age-based preference for young RBCs, were previously demonstrated to be highly resistant to malaria infection. Our study sought to test the therapeutic benefit of CD47 blockade on ameliorating the clinical syndromes of experimental cerebral malaria (ECM), using the Plasmodium berghei ANKA (Pb-A) murine model. In vitro we tested the effect of anti-CD47 mAb on Plasmodium-infected RBC phagocytosis and found that anti-CD47 treatment significantly increased clearance of Plasmodium-infected RBCs. Infection of C57BL/6 mice with Pb-A is lethal and mice succumb to the clinical syndromes of CM between days 6 and 10 postinfection. Strikingly, treatment with anti-CD47 resulted in increased survival during the cerebral phase of Pb-A infection. Anti-CD47-treated mice had increased lymphocyte counts in the peripheral blood and increased circulating levels of IFN-γ, TNF-α, and IL-22. Despite increased circulating levels of inflammatory cytokines, anti-CD47-treated mice had reduced pathological features in the brain. Survival of ECM in anti-CD47-treated mice was correlated with reduced cellular accumulation in the cerebral vasculature, improved blood-brain barrier integrity, and reduced cytotoxic activity of infiltrating CD8+ T cells. These results demonstrate the therapeutic benefit of anti-CD47 to reduce morbidity in a lethal model of ECM, which may have implications for preventing mortality in young African children who are the highest casualties of CM.

  View details for DOI 10.1073/pnas.1907653118

  View details for PubMedID 33836556

  View details for PubMedCentralID PMC7980459

• Neutrophil and monocyte kinetics play critical roles in mouse peritoneal adhesion formation. Blood advances Tsai, J. M., Shoham, M., Fernhoff, N. B., George, B. M., Marjon, K. D., McCracken, M. N., Kao, K. S., Sinha, R., Volkmer, A. K., Miyanishi, M., Seita, J., Rinkevich, Y., Weissman, I. L. 2019; 3 (18): 2713–21

  Abstract

  Peritoneal adhesions are pathological fibroses that ensnare organs after abdominal surgery. This dense connective tissue can cause small bowel obstruction, female infertility, and chronic abdominal pain. The pathogenesis of adhesions is a fibrotic response to tissue damage coordinated between mesothelial cells, fibroblasts, and immune cells. We have previously demonstrated that peritoneal adhesions are a consequence of mechanical injury to the mesothelial layer sustained during surgery. Neutrophils are among the first leukocytes involved in the early response to tissue damage. Here, we show that when subjected to mechanical stress, activated mesothelial cells directly recruit neutrophils and monocytes through upregulation of chemokines such as CXCL1 and monocyte chemoattractant protein 1 (MCP-1). We find that neutrophils within the adhesion sites undergo cell death and form neutrophil extracellular traps (NETosis) that contribute to pathogenesis. Conversely, tissue-resident macrophages were profoundly depleted throughout the disease time course. We show that this is distinct from traditional inflammatory kinetics such as after sham surgery or chemically induced peritonitis, and suggest that adhesions result from a primary difference in inflammatory kinetics. We find that transient depletion of circulating neutrophils significantly decreases adhesion burden, and further recruitment of monocytes with thioglycolate or MCP-1 also improves outcomes. Our findings suggest that the combination of neutrophil depletion and monocyte recruitment is sufficient to prevent adhesion formation, thus providing insight for potential clinical interventions.

  View details for DOI 10.1182/bloodadvances.2018024026

  View details for PubMedID 31519647

• Surgical adhesions in mice are derived from mesothelial cells and can be targeted by antibodies against mesothelial markers. Science translational medicine Tsai, J. M., Sinha, R., Seita, J., Fernhoff, N., Christ, S., Koopmans, T., Krampitz, G. W., McKenna, K. M., Xing, L., Sandholzer, M., Sales, J. H., Shoham, M., McCracken, M., Joubert, L., Gordon, S. R., Poux, N., Wernig, G., Norton, J. A., Weissman, I. L., Rinkevich, Y. 2018; 10 (469)

  Abstract

  Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and are a major cause of postsurgical and infectious morbidity. The primary molecular chain of events leading to the initiation of adhesions has been elusive, chiefly due to the lack of an identifiable cell of origin. Using clonal analysis and lineage tracing, we have identified injured surface mesothelium expressing podoplanin (PDPN) and mesothelin (MSLN) as a primary instigator of peritoneal adhesions after surgery in mice. We demonstrate that an anti-MSLN antibody diminished adhesion formation in a mouse model where adhesions were induced by surgical ligation to form ischemic buttons and subsequent surgical abrasion of the peritoneum. RNA sequencing and bioinformatics analyses of mouse mesothelial cells from injured mesothelium revealed aspects of the pathological mechanism of adhesion development and yielded several potential regulators of this process. Specifically, we show that PDPN+MSLN+ mesothelium responded to hypoxia by early up-regulation of hypoxia-inducible factor 1 alpha (HIF1alpha) that preceded adhesion development. Inhibition of HIF1alpha with small molecules ameliorated the injury program in damaged mesothelium and was sufficient to diminish adhesion severity in a mouse model. Analyses of human adhesion tissue suggested that similar surface markers and signaling pathways may contribute to surgical adhesions in human patients.

  View details for PubMedID 30487249

• Surgical adhesions in mice are derived from mesothelial cells and can be targeted by antibodies against mesothelial markers SCIENCE TRANSLATIONAL MEDICINE Tsai, J. M., Sinha, R., Seita, J., Fernhoff, N., Christ, S., Koopmans, T., Krampitz, G. W., McKenna, K. M., Xing, L., Sandholzer, M., Sales, J., Shoham, M., McCracken, M., Joubert, L., Gordon, S. R., Poux, N., Wernig, G., Norton, J. A., Weissman, I. L., Rinkevich, Y. 2018; 10 (469)

  View details for DOI 10.1126/scitranslmed.aan6735

  View details for Web of Science ID 000451465600001