About

Mary E. Putt, Ph.D., Sc.D., is a Professor of Biostatistics in the Department of Biostatistics and Epidemiology at the Hospital of the University of Pennsylvania, within the Perelman School of Medicine. She is also a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics and serves as Deputy Director of the Division of Biostatistics in the Department of Biostatistics, Epidemiology & Informatics at the University of Pennsylvania Perelman School of Medicine. Her educational background includes a B.S. in Botany from the University of Manitoba, an M.S. and Ph.D. in Biology from McMaster University and the University of California at Santa Barbara respectively, and a Sc.D. in Biostatistics from Harvard School of Public Health. Her research focuses on biostatistics and epidemiology, with significant contributions to clinical epidemiology and statistical methods in medical research. She has authored numerous publications, including studies on neurodevelopment in fetuses with congenital heart defects, risks associated with induced abortion, and statistical significance in clinical research. Dr. Putt's work emphasizes the application of statistical analysis to improve understanding of health outcomes and medical interventions.

Research topics

• Medicine
• Internal medicine
• Physical therapy
• Computer Science
• Nursing
• Medical physics
• Biology
• Emergency medicine
• Environmental health
• Nuclear physics
• Economics
• Optics
• Nuclear engineering
• Physics
• Cardiology
• Engineering
• Pathology
• Cancer research

Selected publications

• Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial

  The Lancet Neurology · 2026-04-17 · 1 citations

  articleOpen access

  BACKGROUND: precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia. METHODS: . Stage 1 analysis tested the difference between each active treatment versus the control group, and stage 2 analysis (if combination therapy was effective) tested the difference between combination treatment and exercise alone; family-wise type 1 error was maintained <0·05. Analyses were by intention-to-treat. Adverse events were recorded systematically. This trial is registered with ClinicalTrials.gov (NCT04192136) and is complete. FINDINGS: =0·0299) for nicotinamide riboside and exercise in combination. Combination therapy was not statistically different from exercise alone (difference -0·05 ([95% CI -0·10 to 0·21]; p=0·49). Adverse events were all mild or moderate, and included gastrointestinal symptoms, falls, upper respiratory infections, and skin rashes. At least one moderate adverse event of interest in these categories was reported by seven (41%) participants in the control group; six (35%) in the nicotinamide riboside and no exercise group; three (19%) in the placebo and exercise group; and four (25%) in the nicotinamide plus exercise group. INTERPRETATION: The combination of nicotinamide riboside plus exercise for 12 weeks was safe and increased cardiopulmonary fitness in children and adults with Friedreich's ataxia. Longer studies are needed to establish whether adding nicotinamide riboside to exercise could be considered as part of a long-term, comprehensive treatment approach. FUNDING: US National Institutes of Health and Friedreich's Ataxia Research Alliance.

  PublisherDOI

• Figure 2 from PD-1 Blockade Mitigates Surgery-Induced Immunosuppression and Increases the Efficacy of Photodynamic Therapy for Pleural Mesothelioma

  2025-05-23

  preprintOpen access

  &lt;p&gt;PD-1 blockade is minimally effective in AB12 and AE17O mouse mesothelioma tumors before or after TI. &lt;b&gt;A,&lt;/b&gt; In subcutaneous AB12 mouse mesothelioma tumors, TI significantly decreased the median tumor growth time to 400 mm&lt;sup&gt;3&lt;/sup&gt; from 7 days compared with 9 days in untreated TC (&lt;i&gt;P&lt;/i&gt; = 0.025). For TC, &lt;i&gt;n&lt;/i&gt; = 17 mice and for TI, &lt;i&gt;n&lt;/i&gt; = 11 mice. &lt;b&gt;B,&lt;/b&gt; The addition of αPD-1 (TC/αPD-1, dotted black line) to TC did not significantly change tumor response (&lt;i&gt;P&lt;/i&gt; = 0.27). In the TC/αPD-1 group, one mouse was censored because of tumor ulceration and subsequent early euthanasia. For TC/αPD-1, &lt;i&gt;n&lt;/i&gt; = 12 mice. &lt;b&gt;C,&lt;/b&gt; The addition of αPD-1 to TI led to significantly better outcomes with a slight delay in the median tumor growth time to 400 mm&lt;sup&gt;3&lt;/sup&gt; (7 days for TI and 11 days for TI/αPD-1; &lt;i&gt;P&lt;/i&gt; = 0.028) For TI/αPD-1, &lt;i&gt;n&lt;/i&gt; = 11 mice. &lt;b&gt;D,&lt;/b&gt; In AE17O tumors, TI produced a modest insignificant increase in tumor growth compared with TC (&lt;i&gt;P&lt;/i&gt; = 0.057 with a median of 13 days for TI vs. 14 days for TC). For TC, &lt;i&gt;n&lt;/i&gt; = 10 mice and for TI, &lt;i&gt;n&lt;/i&gt; = 11 mice. &lt;b&gt;E,&lt;/b&gt; Adding αPD-1 in AE17O TC mice delayed the median time for tumor growth to 400 mm&lt;sup&gt;3&lt;/sup&gt; by 1 week from 14 days in TC mice to 21 days after TC/αPD-1 (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). For TC/αPD-1, &lt;i&gt;n&lt;/i&gt; = 12 mice. &lt;b&gt;F,&lt;/b&gt; The addition of αPD-1 to TI also led to significantly better outcomes with a median time to 400 mm&lt;sup&gt;3&lt;/sup&gt; increasing from 13 days after TI to 17 days for TI/αPD-1 (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). For TI/αPD-1, &lt;i&gt;n&lt;/i&gt; = 12 mice. &lt;b&gt;G&lt;/b&gt; and &lt;b&gt;H,&lt;/b&gt; In AB12 tumors, flow cytometry of TC and TI tumors found a significant drop in PD-1 levels 2 days after a single αPD-1 dose for (&lt;b&gt;G&lt;/b&gt;) CD4&lt;sup&gt;+&lt;/sup&gt; T cells and (&lt;b&gt;H&lt;/b&gt;) CD8&lt;sup&gt;+&lt;/sup&gt; T cells. For TC &lt;i&gt;n&lt;/i&gt; = 11 tumors, for TC/αPD-1 &lt;i&gt;n&lt;/i&gt; = 11 tumors, for TI &lt;i&gt;n&lt;/i&gt; = 14 tumors, and for TI/αPD-1 &lt;i&gt;n&lt;/i&gt; = 10 tumors. Tumor responses (time to 400 mm&lt;sup&gt;3&lt;/sup&gt;) are compared using a log-rank (Mantel–Cox) test; comparisons of continuous outcomes used a Mann–Whitney test.&lt;/p&gt;

  PublisherDOI

• Table 1 from PD-1 Blockade Mitigates Surgery-Induced Immunosuppression and Increases the Efficacy of Photodynamic Therapy for Pleural Mesothelioma

  2025-05-23

  preprintOpen access

  &lt;p&gt;Characteristics of patients (&lt;i&gt;n&lt;/i&gt; = 31) whose PM specimens were used for RNA-seq analysis&lt;/p&gt;

  PublisherDOI

• Concern for the validity of short-term dietary crossover trials

  Nature Medicine · 2025-08-22 · 2 citations

  letterSenior author
  PublisherDOI

• Figure 4 from PD-1 Blockade Mitigates Surgery-Induced Immunosuppression and Increases the Efficacy of Photodynamic Therapy for Pleural Mesothelioma

  2025-05-23

  preprintOpen access

  &lt;p&gt;TI increases PD-1 expression on AB12 intratumoral T cells. &lt;b&gt;A,&lt;/b&gt; In AB12 tumors, 2 days after TI, the fraction of CD4 and CD8 T cells (as a percentage of all CD3&lt;sup&gt;+&lt;/sup&gt; cells) was not significantly different between TI (&lt;i&gt;n&lt;/i&gt; = 11) and TC (&lt;i&gt;n&lt;/i&gt; = 14). However, the levels of DX5+ (NKT cells) decreased slightly but significantly in TI (&lt;i&gt;P&lt;/i&gt; = 0.017). &lt;b&gt;B,&lt;/b&gt; For all CD3&lt;sup&gt;+&lt;/sup&gt; cells, the levels of PD-1 were significantly upregulated by TI compared with TC (&lt;i&gt;P&lt;/i&gt; = 0.009). &lt;b&gt;C,&lt;/b&gt; For individual T-cell populations, PD-1 was significantly increased in CD8&lt;sup&gt;+&lt;/sup&gt; (&lt;i&gt;P&lt;/i&gt; = 0.001) and DX5+ (&lt;i&gt;P&lt;/i&gt; = 0.006) T cells after TI compared with TC. &lt;b&gt;D,&lt;/b&gt; After 5 days, TC and TI tumors have similar numbers of CD8, CD4, and DX5+ T cells. For CD4 and CD8 T cells, &lt;i&gt;n&lt;/i&gt; = 11 for TC and &lt;i&gt;n&lt;/i&gt; = 11 for TI. For NKT cells, &lt;i&gt;n&lt;/i&gt; = 8 for TI and &lt;i&gt;n&lt;/i&gt; = 8 for TC. &lt;b&gt;E,&lt;/b&gt; For all CD3&lt;sup&gt;+&lt;/sup&gt; cells, significant differences in median PD-1 levels were not detected at the 5-day time point (&lt;i&gt;P&lt;/i&gt; = 0.098). &lt;b&gt;F,&lt;/b&gt; CD4&lt;sup&gt;+&lt;/sup&gt; T cells had significantly higher PD-1 expression 5 days after TI (&lt;i&gt;P&lt;/i&gt; = 0.049). Differences in PD-1 expression of CD8 and DX5 T cells at 5 days after TI were small and not statistically significant. Comparisons were made using a Mann–Whitney test. FMO, fluorscence minus one.&lt;/p&gt;

  PublisherDOI

• Supplementary Figure 8 from PD-1 Blockade Mitigates Surgery-Induced Immunosuppression and Increases the Efficacy of Photodynamic Therapy for Pleural Mesothelioma

  2025-05-23

  preprintOpen access

  &lt;p&gt;PD1 and Ly6G depletion&lt;/p&gt;

  PublisherDOI

• Proceedings of the University of Pennsylvania 16th annual conference on statistical issues in clinical trials: Optimizing dose selection across the clinical trials spectrum

  Clinical Trials · 2025-06-10 · 1 citations

  articleOpen access1st authorCorresponding
  PublisherDOI

• Sleep drive, not total sleep amount, increases seizure risk

  Nature Communications · 2025-07-29 · 4 citations

  articleOpen access

  Sleep loss has been associated with increased seizure risk since antiquity. Using automated video detection of spontaneous seizures in Drosophila epilepsy models, we show that seizures worsen only when sleep restriction raises homeostatic "sleep drive," not simply when total sleep amount falls. This is supported by the paradoxical finding that acute activation of sleep-promoting circuits worsens seizures, because it increases sleep drive without changing sleep amount. Sleep-promoting circuits become hyperactive after sleep loss and are associated with increased whole-brain activity. During sleep restriction, optogenetic inhibition of sleep-promoting circuits to reduce sleep drive protects against seizures. Downregulation of the 5HT1A serotonin receptor in sleep-promoting cells mediates the effect of sleep drive on seizures, and we identify an FDA-approved 5HT1A agonist to mitigate seizures. Our findings demonstrate that while homeostatic sleep is needed to recoup lost sleep, sleep drive comes at the cost of increasing seizure susceptibility.

  PublisherOA PDFDOI

• Prearrest vital sign abnormalities are associated with adverse outcomes in pediatric ICU cardiac arrest: a get with the guidelines-resuscitation analysis

  Resuscitation · 2025-09-25

  articleOpen access

  AIM: We aimed to quantitatively describe vital sign abnormalities prior to pediatric IHCA and evaluate whether the severity of abnormalities was independently associated with survival. METHODS: In a retrospective cohort study using the American Heart Association's Get with The Guidelines-Resuscitation® registry, children with ≥1 min of cardiopulmonary resuscitation (CPR) in an Intensive Care Unit (ICU) from 2007 to 2022 with prearrest vital signs were included. Vital signs most proximate to CPR (10-120 min prior) were classified as abnormal (HR or RR >95th, SBP or DBP <5th percentile for age). Multivariable regression adjusted for age, illness category, prearrest conditions, and prearrest interventions assessed the associations between vital sign abnormalities and outcomes (primary: survival to hospital discharge, secondary: return of spontaneous circulation [ROSC]). RESULTS: Of 2875 IHCA patients meeting inclusion criteria, 1790 (62.3 %) had at least one abnormal vital sign. Patients with vital sign abnormalities were older, had non-surgical illness categories, and higher prevalence of prearrest illnesses and interventions. Low SBP (<5%) was the vital sign with the lowest odds of survival to hospital discharge (aOR 0.56 [95 %CI 0.46-0.68], p < 0.01) and ROSC (aOR 0.63 [95 %CI 0.54-0.73], p < 0.01). There was a stepwise decrease in the adjusted odds of survival for each additional abnormal vital sign (1 vs 0: aOR 0.62 [95 %CI 0.51-0.76], p < 0.01; 2 vs 1: 0.72 [95 %CI 0.53-0.97] p = 0.03; 3 vs 2: 0.53 [95 %CI 0.33-0.86] p < 0.01). CONCLUSIONS: Prearrest vital sign abnormalities are common in pediatric ICU IHCA and independently associated with worse outcomes, emphasizing the need for prompt detection and intervention to improve outcomes.

  PublisherDOI

• Data from PD-1 Blockade Mitigates Surgery-Induced Immunosuppression and Increases the Efficacy of Photodynamic Therapy for Pleural Mesothelioma

  2025-05-23

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;Lung-sparing radical pleurectomy with intraoperative photodynamic therapy (PDT) demonstrates remarkable survival for patients with pleural mesothelioma. Nevertheless, most patients treated with this multimodal approach will develop local tumor recurrence. An understanding of potential causes of treatment failure is central to developing mitigation strategies. Surgery importantly reduces disease burden but also produces tumor-promoting inflammation, as demonstrated through transcriptomic analysis of pleural mesothelioma specimens. Using preclinical models in the setting of combination therapy, we separated the benefit of surgical resection from its counterproductive effects on therapeutic outcome. Specifically, we evaluated mechanisms by which surgically induced inflammation can be therapy-limiting in a murine model of tumor incision (TI) introduced by a surgical cut across the tumor. In this TI model, we identified distinct TI-altered patterns in innate and adaptive inflammatory cells in murine mesothelioma tumors, and we studied changes in these patterns with the addition of PDT. TI introduction of an immunosuppressive environment is established via upregulation of PD-1/PD-L1 expression on tumor cells, T cells, and myeloid cells that is partially resolved by PDT. Immune dysfunction is further mitigated by the addition of PD-1 blockade, leading to curative potential in a process that requires Ly6G&lt;sup&gt;+&lt;/sup&gt; neutrophils and CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Overall, these studies suggest that, without PDT, surgical modulation of immune cell trafficking and functionality leads to systemic immunosuppression. This immunosuppressive state potentially interferes with the generation of antitumor immunity by PDT. However, targeted inhibition of surgery-induced signaling in the PD-l/PD-L1 pathway counteracts surgery’s immunosuppressive outcomes to enhance PDT efficacy in the intraoperative setting.&lt;/p&gt;Significance:&lt;p&gt;Surgery combined with PDT extends survival for patients with mesothelioma, but these patients are still at risk for tumor recurrence, in part due to the immunosuppressive effects of surgery. We find, in a mouse model, that combining surgery, PDT, and immune checkpoint blockade maximizes the efficacy of these therapies.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

Recent grants

• Analytical Neurochemistry: Core D

  NIH · $12.7M · 2021

• NIH Grant P01CA087971

  NIH · $28.4M · 2022

• NIH Grant P30HD026979

  NIH · $31.5M · 2015

Frequent coauthors

• Theresa M. Busch

  99 shared

• Keith A. Cengel

  University of Pennsylvania

  86 shared

• Michele M. Kim

  University of Pennsylvania

  72 shared

• Bonnie Ky

  63 shared

• Stephen E. Kimmel

  University of Florida

  55 shared

• Thomas P. Cappola

  University of Pennsylvania Health System

  55 shared

• Gwendolyn M. Cramer

  53 shared

• James M. Metz

  50 shared

Labs

• Biostatistics and EpidemiologyPI

Awards & honors

• Senior Scholar, Center for Clinical Epidemiology and Biostat…