Current Research

Palestine Program for Health and Human Rights

Are hospitals collateral damage? Assessing geospatial proximity of 2000 lb bomb detonations to hospital facilities in the Gaza Strip from October 7 to November 17, 2023

Kunichoff, D., Mills, D., Asi, Y., Abdulrahim, S., Wispelwey, B., Tanous, O., Ahmed, A. K., Hammoudeh, W., Bahour, N., Bassett, M. T., & Greenough, P. G. (2024). Are hospitals collateral damage? Assessing geospatial proximity of 2000 lb bomb detonations to hospital facilities in the Gaza Strip from October 7 to November 17, 2023. PLOS global public health, 4(10), e0003178. https://doi.org/10.1371/journal.pgph.0003178

After attacks in Israel led by Hamas militants on October 7, 2023, Israel launched a major military campaign in the Gaza Strip that has featured an unprecedented scale of destruction. This has included the use of highly destructive weapons in a densely populated area. Mark-84 bombs (M-84s) are 2000 lb air-dropped explosive munitions with the capacity to damage infrastructure and kill or cause severe injury hundreds of meters away. This study examines the proximity of M-84 bomb detonations to hospital infrastructure in the Gaza Strip. We combined geospatial data on hospital locations across the Gaza Strip with maps of the locations of M-84 bomb craters between October 7 and November 17, 2023, published by CNN and New York Times. We then measured and summarized the proximity of the bomb craters to hospitals across the territory. We identified 592 M-84 bomb craters. Of the 36 hospitals across the Gaza Strip, 25% (n = 9) had at least one bomb crater within the lethal range (360 m) and 83.3% (n = 30) within the infrastructure damage and injury range (800 m) of their facilities. The shortest distance of a bomb crater from a hospital was 14.7 m. Two hospitals had as many as 23 and 21 bomb craters within 800 m of their facilities and one hospital had seven bomb craters within 360 m. Thirty-eight M-84 bombs were detonated within 800 m of hospitals in the Israeli military defined evacuation zone. Given the known blast effect of these M-84 bombs, the impact from the bomb detonations near hospitals likely killed and injured people in and around the hospital area, which could include civilians and hospital staff, and likely damaged hospital infrastructure. The results of this study suggest indiscriminate bombing in dangerous proximities to hospital infrastructure, which is afforded special protection under international humanitarian law (IHL).

‘Nowhere and no one is safe’: spatial analysis of damage to critical civilian infrastructure in the Gaza Strip during the first phase of the Israeli military campaign, 7 October to 22 November 2023

Asi, Y., Mills, D., Greenough, P. G., Kunichoff, D., Khan, S., Hoek, J. V. D., Scher, C., Halabi, S., Abdulrahim, S., Bahour, N., Ahmed, A. K., Wispelwey, B., & Hammoudeh, W. (2024). 'Nowhere and no one is safe': spatial analysis of damage to critical civilian infrastructure in the Gaza Strip during the first phase of the Israeli military campaign, 7 October to 22 November 2023. Conflict and Health, 18(1), 24–24. https://doi.org/10.1186/s13031-024-00580-x

Background: Since the Hamas attacks in Israel on 7 October 2023, the Israeli military has launched an assault in the Gaza Strip, which included over 12,000 targets struck and over 25,000 tons of incendiary munitions used by 2 November 2023. The objectives of this study include: (1) the descriptive and inferential spatial analysis of damage to critical civilian infrastructure (health, education, and water facilities) across the Gaza Strip during the first phase of the military campaign, defined as 7 October to 22 November 2023 and (2) the analysis of damage clustering around critical civilian infrastructure to explore broader questions about Israel’s adherence to International Humanitarian Law (IHL).

Methods: We applied multi-temporal coherent change detection on Copernicus Sentinel 1-A Synthetic Aperture Radar (SAR) imagery to detect signals indicative of damage to the built environment through 22 November 2023. Specific locations of health, education, and water facilities were delineated using open-source building footprint and cross-checked with geocoded data from OCHA, OpenStreetMap, and Humanitarian OpenStreetMap Team. We then assessed the retrieval of damage at and with close proximity to sites of health, education, and water infrastructure in addition to designated evacuation corridors and civilian protection zones. The Global Moran’s I autocorrelation inference statistic was used to determine whether health, education, and water facility infrastructure damage was spatially random or clustered.

Results: During the period under investigation, in the entire Gaza Strip, 60.8% (n = 59) of health, 68.2% (n = 324) of education, and 42.1% (n = 64) of water facilities sustained infrastructure damage. Furthermore, 35.1% (n = 34) of health, 40.2% (n = 191) of education, and 36.8% (n = 56) of water facilities were functionally destroyed. Applying the Global Moran’s I spatial inference statistic to facilities demonstrated a high degree of damage clustering for all three types of critical civilian infrastructure, with Z-scores indicating < 1% likelihood of cluster damage occurring by random chance.

Conclusion: Spatial statistical analysis suggests widespread damage to critical civilian infrastructure that should have been provided protection under IHL. These findings raise serious allegations about the violation of IHL, especially in light of Israeli officials’ statements explicitly inciting violence and displacement and multiple widely reported acts of collective punishment.

Past Projects

Hotamışlıgil Lab at the Sabri Ülker Center

Endogenous p53 inhibitor TIRR dissociates systemic metabolic health from oncogenic activity

Tsaousidou, E., Chrzanowski, J., Drané, P., Lee, G. Y., Bahour, N., Wang, Z. B., Deng, S., Cao, Z., Huang, K., He, Y., Kaminski, M., Michalek, D., Güney, E., Parmar, K., Fendler, W., Chowdhury, D., & Hotamışlıgil, G. S. (2024). Endogenous p53 inhibitor TIRR dissociates systemic metabolic health from oncogenic activity. Cell reports, 43(6), 114337. https://doi.org/10.1016/j.celrep.2024.114337

It is unclear whether metabolic health corresponds to reduced oncogenesis or vice versa. We study Tudor-interacting repair regulator (TIRR), an inhibitor of p53 binding protein 1 (53BP1)-mediated p53 activation, and the physiological consequences of enhancing tumor suppressor activity. Deleting TIRR selectively activates p53, significantly protecting against cancer but leading to a systemic metabolic imbalance in mice. TIRR-deficient mice are overweight and insulin resistant, even under normal chow diet. Similarly, reduced TIRR expression in human adipose tissue correlates with higher BMI and insulin resistance. Despite the metabolic challenges, TIRR loss improves p53 heterozygous (p53HET) mouse survival and correlates with enhanced progression-free survival in patients with various p53HET carcinomas. Finally, TIRR's oncoprotective and metabolic effects are dependent on p53 and lost upon p53 deletion in TIRR-deficient mice, with glucose homeostasis and orexigenesis being primarily regulated by TIRR expression in the adipose tissue and the CNS, respectively, as evidenced by tissue-specific models. In summary, TIRR deletion provides a paradigm of metabolic deregulation accompanied by reduced oncogenesis.

FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection

Baazim, H., Koyuncu, E., Tuncman, G., Burak, M. F., Merkel, L., Bahour, N., Karabulut, E., Lee, G. Y., Hanifehnezhad, A., Karagoz, Z. F., Foldes, K., Ilayda Engin, Ayse Gokce Erman, Oztop, S., Filazi, N., Gul, B., Ceylan, A., Cinar, O. O., Can, F., … Hotamisligil, G. S. (2024). FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection. bioRxiv. https://doi.org/10.1101/2024.02.10.579717

Host metabolic fitness is a critical determinant of infectious disease outcomes. In COVID-19, obesity and aging are major high-risk disease modifiers, although the underlying mechanism remains unknown. Here, we demonstrate that fatty acid binding protein 4 (FABP4), a critical regulator of metabolic dysfunction in these conditions, regulates SARS-CoV2 pathogenesis. Our study revealed that elevated FABP4 levels in COVID-19 patients strongly correlate with disease severity. In adipocytes and airway epithelial cells we found that loss of FABP4 function by genetic or pharmacological means impaired SARS-CoV2 replication and disrupted the formation of viral replication organelles. Furthermore, treatment of infected hamsters with FABP4 inhibitors alleviated lung damage and fibrosis and reduced lung viral titers. These results highlight a novel host factor critical for SARS-CoV2 infection and the therapeutic potential of FABP4-targeting agents in treating COVID-19 patients.

Beta Cell Aging Lab

Implication of Senolysis in Beta Cell Replication and Mass

Bahour N, Bleichmar L, Abarca C, Wilmann E, Sanjines S, Aguayo-Mazzucato C, . Clearance of p16Ink4a-positive cells in a mouse transgenic model does not change β-cell mass and has limited effects on their proliferative capacity. Aging (Albany NY). 2023 Jan 12; . https://doi.org/10.18632/aging.204483

Type 2 diabetes is partly characterized by decreased β-cell mass and function which have been linked to cellular senescence. Despite a low basal proliferative rate of adult β-cells, they can respond to growth stimuli, but this proliferative capacity decreases with age and correlates with increased expression of senescence effector, p16Ink4a. We hypothesized that selective deletion of p16Ink4a-positive cells would enhance the proliferative capacity of the remaining β-cells due to the elimination of the local senescence-associated secretory phenotype (SASP). We aimed to investigate the effects of p16Ink4a-positive cell removal on the mass and proliferative capacity of remaining β-cells using INK-ATTAC mice as a transgenic model of senolysis. Clearance of p16Ink4a positive subpopulation was tested in mice of different ages, males and females, and with two different insulin resistance models: high-fat diet (HFD) and insulin receptor antagonist (S961). Clearance of p16Ink4a-positive cells did not affect the overall β-cell mass. β-cell proliferative capacity negatively correlated with cellular senescence load and clearance of p16Ink4a positive cells in 1-year-old HFD mice improved β-cell function and increased proliferative capacity in a subset of animals. Single-cell sequencing revealed that the targeted p16Ink4asubpopulation of β-cells is non-proliferative and non-SASP producing whereas additional senescent subpopulations remained contributing to continued local SASP secretion. In conclusion, deletion of p16Ink4a cells did not negatively impact beta-cell mass and blood glucose under basal and HFD conditions and proliferation was restored in a subset of HFD mice opening further therapeutic targets in the treatment of diabetes.

Diabetes Mellitus correlates with increased biological age as indicated by clinical biomarkers

Bahour, N., Cortez, B., Pan, H. et al. Diabetes mellitus correlates with increased biological age as indicated by clinical biomarkers. GeroScience (2021). doi.org/10.1007/s11357-021-00469-0

Chronological age (CA) is the age given in years since birth whereas biological age (BA) is based on quantifiable changes on a cellular level measured through biomarkers. BA has a strong correlation with morbidity and mortality accounting for individual differences in the rate of aging and longevity. Since type 2 diabetes (T2D) is associated with increased morbidity and mortality, we hypothesized that BA would be increased in T2D diagnosed individuals and could be calculated with biomarkers from routine visits. In this study, we obtained deidentified data from three cohorts: (1) T2D (n= 686), (2) T1D (n= 540) (as a metabolic control) from Joslin Diabetes Center and (3) nondiabetics (n= 522) from the 2017-2018 National Health and Nutrition Examination Survey. Ages ranged from 20-80 years and for analysis, persons with diabetes were matched by age and gender to subjects without diabetes. Eight clinical biomarkers significantly correlated with CA in people without diabetes (p-values from 1.1 x10-98 to 5.6 x10-3). The Klemera and Doubal method (KDM) was used to calculate BA and results were confirmed using multiple linear regression. We observed a strong correlation between CA and BA in people without diabetes (R2 = 0.94, p< 0.0001) validating the biomarkers and KDM in our population. BA of people with T2D was, on average, 12 years higher than people without diabetes (p= 5.2 x10- 187). BA of people with T1D was 15 years higher (p= 2.3 x10- 236). The biomarkers with the strongest correlation to increased BA in T2D were systolic blood pressure (R2= 0.29, p< 2 x10- 16) and A1c (R2= 0.27, p< 2 x10-16), suggesting that BA is dynamic and can be modified. Linear regression confirmed a significant increase of BA in persons with diabetes. In conclusion, increased BA in people with diabetes suggests accelerated aging, a critical concept for integrating the cellular understanding of aging with the environment and which can enhance future research on the relation between aging biology and diabetes.

Biological Age in Diabetes and Precision Medicine

Cortez, B, Bahour, N, Aguayo-Mazzucato, C. Biological age in diabetes and precision medicine. Aging (2022). doi.org/10.18632/aging.204123 [Epub ahead of print]