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Mithun Shah, MD, PhD

Mayo clinic, titles + affiliations.

Hematology Specialist Mayo Clinic

Predicting and Preventing Therapy-Related Myeloid Neoplasm in Multiple Myeloma Patients Undergoing Stem Cell Transplantation

Therapy-related myeloid neoplasm (t-MN) is a leukemia that develops following DNA-damaging therapies. t-MN is one of the most aggressive malignancies with no effective therapies, making early prediction and prevention critical. Multiple myeloma (MM) patients who develop t-MN after undergoing stem cell transplantation (SCT) provide a unique insight into t-MN pathogenesis. MM patients are at 12-fold higher risk of t-MN compared to general population, suggesting genetic predisposition. This risk increases to 100-fold in patients undergoing SCT, suggesting that selection pressure exerted by chemotherapy also contributes to t-MN. We performed targeted sequencing and methylation analysis using paired samples obtained pre-SCT and at t-MN diagnosis and showed that those that develop t-MN (cases) have a unique genetic and methylation profile compared to matched-controls years prior to developing t-MN. Whether pharmacological intervention targeting these differences can prevent and treat t-MN is not known. In aim 1, we will investigate if hematopoietic stem cell (HSC)-intrinsic factors such as TP53-defiient state and spindle assembly checkpoint (SAC) may be present years prior to leukemic transformation, and whether SAC inhibitors can be used for prevention or therapy. In aim 2, we will study how melphalan, directly or by increasing 8-oxoguanine incorporation, predisposes to chromosomal breaks. We will study if MTH1 inhibitor, by reducing 8-oxoG incorporation prevents t-MN.

With the help of the Leukemia Research Foundation New Investigator Award, I have made significant progress towards setting up an independent and sustainable research program focusing on the improving outcomes for patients with therapy-related myeloid neoplasms (t-MN).  I have established deep collaborations with leaders in the field, significantly strengthening research capabilities. The Award has facilitated publication of manuscripts and presentations. The generous Leukemia Research Foundation funding has allowed me to generate exciting preliminary data and recruit motivated personnel. With that, I was able to submit two Department of Defense grants in the year 2022. My current goal is to submit to R-01 grants in the first half of 2023. These research projects will address one of the largest unmet needs of the leukemia field -- the development of the TP53mut leukemia. Given its increasing prevalence and abysmal outcomes, improving the outcomes of TP53mut leukemia is critical in improving outcomes of leukemia in general.

Leukemia Research Foundation grant $100K awarded in 2021

Disease focus Acute myeloid leukemia (AML) Myelodysplastic syndromes (MDS)

Research focus Causes/risk factors (MDS)

Trish Jeanne Simner , PhD

• Johns Hopkins School of Medicine Faculty

Primary Academic Title

Professor of Pathology

Dr. Patricia (Trish) Simner received her Ph.D. in 2011 at the University of Manitoba in Winnipeg, Manitoba, Canada.  Her Ph.D. research was funded by the successful application for the prestigious Alexander Graham Bell Canadian Graduate Scholarship Award from the Natural Sciences and Engineering Research Council in Ottawa, Ontario, Canada.   In Dr. Simner's thesis work, she studied the epidemiology and molecular characterization of ESBL- and AmpC β-lactamase-producing Enterobacteriaceae isolated in Canadian hospitals from 2005-2009.  Her work as part of the Canadian Antimicrobial Resistance Alliance has resulted in a total of 25 peer-reviewed publications from 2007 to date with greater than 30 abstract presentations at national and international conferences.  From her Ph.D. work she is a known researcher in the area of mechanism of antibiotic resistance, in particular β-lactam resistance among Gram-negative bacteria.

After obtaining her Ph.D., Dr. Simner completed a two year Clinical Microbiology Fellowship at the world renowned Mayo Clinic in Rochester, MN.   During her time at the Mayo Clinic she was involved in the evaluation, development and implementation of novel molecular diagnostic tools such as matrix-assisted laser-desorption ionization time-of-flight mass spectrometry and polymerase chain reaction electrospray ionization mass spectrometry.  Her time at the Mayo Clinic was very productive and resulted in 6 book chapters, 5 national and international conference presentations, 4 peer-reviewed publications, 2 case-reports and 1 invited review article.  In addition, she was promoted to Assistant Professor of Laboratory Medicine and Pathology at the Mayo School of Graduate Education due to her excellence in teaching and mentoring.  At the completion of her Clinical Microbiology Fellowship she became board-certified in Medical Microbiology by the American Board of Medical Microbiology. From her fellowship work she is known in the Clinical Microbiology field for developing and evaluating novel diagnostic platforms.

At the completion of her fellowship Dr. Simner returned to her home Province in Manitoba, Canada and worked as a Clinical Microbiologist at St. Boniface Hospital and as an Assistant Professor at the University of Manitoba in the Department of Infectious Diseases and Medical Microbiology for 13 months.  She continued her research focus on antimicrobial resistance mechanisms and her collaborations with the Canadian Antimicrobial Resistance Alliance.  She was able to continue her productivity during this transition period with two peer-reviewed publications.

From there Dr. Simner was welcomed as Assistant Professor of Pathology and Director of the Bacteriology and Parasitology sections of the Medical Microbiology Laboratory in March, 2015.  In her short time at Johns Hopkins she has submitted multiple grant submissions, publications and is involved in interdisciplinary research collaborations. Dr. Simner continues her research in the areas of gram-negative bacterial resistance mechanisms with a focus on carbapenem-resistant gram-negative bacilli and novel diagnostic tools for infectious diseases such as next-generation sequencing.

Dr. Simner is also active in the Clinical Microbiology communities by participating on committees and as a reviewer for the Journal of Clinical Microbiology.

Additional Academic Titles

Joint Appointment in Medicine

http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/47778195

Selected Publications

Simner PJ, SP Buckwalter, JR Uhl and NL Wengenack. 2013. Identification of Mycobacterium species and Mycobacterium tuberculosis Complex Resistance Determinants Using PCR-Electrospray Ionization Mass Spectrometry. J Clin Microbiol. 51:3492-8.

Gniadek T, KC Carroll and PJ Simner. 2016.  Carbapenem-Resistant Glucose Non-Fermenting Gram-Negative Bacilli: The Missing Piece to the Puzzle. J Clin Microbiol. In press.

Goodman K, PJ Simner, PD Tamma and A Milestone. 2015. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE). Expert Rev Anti Infect Ther. Jan;14(1):95-108.

Simner PJ, H Adam, M Baxter, M McCraken, G. Golding, JA Karlowksy, K Nichol, P Lagacé-Wiens, MW Gilmour, Canadian Antimicrobial Resistance Alliance-CARA, DJ Hoban and GG Zhanel. 2015. Epidemiology of Vancomycin-Resistant Enterococci (VRE) in Canadian Hospitals: CANWARD 2007-2013. Antimicrob. Agents Chemotherapy. 59:4315-7.

Simner PJ, H Adam, M Baxter, M McCraken, G. Golding, JA Karlowksy, K Nichol, P Lagacé-Wiens, MW Gilmour, Canadian Antimicrobial Resistance Alliance-CARA, DJ Hoban and GG Zhanel. 2015. Epidemiology of Vancomycin-Resistant Enterococci (VRE) in Canadian Hospitals: CANWARD 2007-2013. Submitted to Antimicrob. Agents Chemotherapy.

Simner PJ, I Martin, B Opene, PD Tamma, KC Carroll and A Milestone. 2016. Point-Prevalence Study and Evaluation of Multiple Methods for the Detection of Gastrointestinal Colonization of Carbapenem-Resistant Organisms from Rectal Swabs in High-Risk Patient Populations. J Clin Microbiol. Submitted to JCM.

Simner PJ, JR Uhl, L Hall, MM Weber, RC Walkchak, S Buckwalter and NL Wengenack. 2013. Broad-Range Direct Detection and Identification of Fungi Using the PLEX-ID PCR-Electrospray Ionization Mass Spectrometry (ESI-MS) System. J Clin Microbiol. 51:1699-1706.

Simner PJ, JR Uhl, L Hall, MM Weber, RC Walkchak, S Buckwalter and NL Wengenack. 2013.  Broad-Range Direct Detection and Identification of Fungi Using the PLEX-ID PCR-Electrospray Ionization Mass Spectrometry (ESI-MS) System.  J Clin Microbiol. 51:1699-1706.

Simner PJ, MW Gilmour, P DeGagne, K Nichol and JA Karlowsky. 2014. Evaluation of Five Chromogenic Agar Media and the Rosco Rapid Carb Screen Kit for Detection and Confirmation of Carbapenemase Production in Gram-Negative Bacilli. J Clin Microbiol. 53:105-12.

Simner PJ, MW Gilmour, P DeGagne, K Nichol and JA Karlowsky.  2014. Evaluation of Five Chromogenic Agar Media and the Rosco Rapid Carb Screen Kit for Detection and Confirmation of Carbapenemase Production in Gram-Negative Bacilli.  J Clin Microbiol. 53:105-12.

Simner PJ, SP Buckwalter, JR Uhl, NL Wengenack and BS Pritt. 2013. Detection and Identification of Yeasts from Formalin-Fixed, Paraffin-Embedded Tissue Using PCR-Electrospray Ionization. J Clin Microbiol. 51:3731-4.

Simner PJ, SP Buckwalter, JR Uhl, NL Wengenack and BS Pritt.  2013. Detection and Identification of Yeasts from Formalin-Fixed, Paraffin-Embedded Tissue Using PCR-Electrospray Ionization. J Clin Microbiol. 51:3731-4.

Suwantarat N, L Logan, KC Carroll, RA Bonomo, PJ Simner, S Rudin, AM Milstone, T. Tekle, T. Ross, and PD Tamma. 2016. The Prevalence and Molecular Characterization of Multidrug-Resistant Enterobacteriaceae Colonization in a Pediatric Intensive Care Unit. Infect Control Hosp Epidemiol. In press.

Tamma PD, N Suwantarat, S Rudin, L Logan, PJ Simner, L Rojas Coy, MF Mojica, KC Carroll and RA Bonomo. 2016. First Report of a VIM metallo-β-lactamase-producing Klebsiella pneumoniae in a Child in the United States. J. Pediatric Infect Dis Soc. In press.

Vasoo, S, S Cunningham, P Kohner, PJ Simner, JN Mandrekar, K Lolans, MK Hayden, and R Patel. 2013. Comparison of a Novel, Rapid Chromogenic Biochemical Assay, the Carba NP Test with the Modified Hodge Test for Detection of Carbapenemase-Producing Gram-Negative Bacilli. J Clin Microbiol. 51:3097-101.

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University of manitoba, board certifications, american board of medical microbiology.

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When the Third Time Is Not the Charm—Trial Outcomes in Idiopathic Pulmonary Fibrosis

• 1 Department of Internal Medicine, Division of Respiratory Medicine, Mayo Clinic, Phoenix, Arizona
• 2 Interstitial Lung Disease Clinic, Mayo Clinic, Phoenix, Arizona
• 3 Center for Individualized Medicine, Mayo Clinic, Phoenix, Arizona
• 4 Associate Editor, JAMA
• 5 Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota
• 6 Interstitial Lung Disease Clinic, Mayo Clinic, Rochester, Minnesota
• Original Investigation Pamrevlumab for Idiopathic Pulmonary Fibrosis Ganesh Raghu, MD; Luca Richeldi, MD; Evans R. Fernández Pérez, MD; Maria Cristina De Salvo, MD; Rafael S. Silva, MD; Jin Woo Song, MD; Takashi Ogura, MD; Zuo Jun Xu, MD; Elizabeth A. Belloli, MD; Xueping Zhang, PhD; Lorilyn L. Seid, MD; Lona Poole, MD; ZEPHYRUS-1 Study Investigators; Simon  Bowler; Tamera  Corte; Mark  Holmes; Francis  Thien; John  Wheatley; Sun-Mi  Choi; Man-Pyo  Chung; Sunghwan  Jeong; Yonghyun  Kim; Eun-Joo  Lee; Hyun-Kyung  Lee; Choonsik  Park; Jong Sun  Park; Joo Hun  Park; David  Chi-Leung Lam; Ming-Cheng  Chan; Kang-Yun  Lee; Jie  Cao; Juan  Chen; Rongchang  Chen; Huaping  Dai; Xiuhua   Fu; Zongan   Liang; Qun   Luo; Guochao  Shi; Zhaohui  Tong; Limin  Wang; Shuanying  Yang; Hongtao  Yu; Huilan  Zhang; Jianchu  Zhang; Hui  Zhao; Wei  Wang; Ying  Meng; Hong  Peng; Murali  Ramaswamy; Mark   Hamblin; John  Fitzgerald; Nishant  Gupta; Jane  Dematte; Srihari  Veeraraghavan; Thomas  O’Brien; Tracy  Luckhardt; Lisa  Lancaster; Marta  Kokoszynska; Neil  Ettinger; Thomas D. Kaelin Jr; Ather  Siddiqi; Bridget  Collins; Mary Beth  Scholand; Danielle   Antin-Ozerkis; Kim  Hyun; Christopher  Harden; Frank  Averill; Jorge  Mallea; Rebecca  Bascom; Vandana  Seeram; Amy  Hajari Case; Edward  Britt; Barry  Shea; Gerard  Criner; Mark  Gotfried; Yolanda  Mageto; Sherif  El Bayadi; Cristina  Reichner; Joshua  Mooney; David  Hotchkin; Rodeo  Abrencillo; Ryan  Boente; Joyce  Lee; Alan  Betensley; Niranjan  Jeganathan; Rajat  Walia; Timothy  Albertson; Ivan  Rosas; Dileep  Puppala; Ladly  Abraham; Richard  Enelow; Nitin  Bhatt; Debabratra  Bandyopadhyay; Pedro Carlos  Elias; Miguel  Bergna; Gabriel Ricardo  Garcia; Gaston  De Stefano; Luis Arturo  Wehbe; Alejandro  Chirino; Ramon  Rojas; Maria  Otaola; Georgina  Miranda; Matias  Florenzano; Rafael  Silva Orellana; Valeska  Glasinovich; Olga  Shangina; Alexey  Nikishenkov; Natalia  Kuzubova JAMA

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that inevitably results in respiratory failure and death within 3 to 5 years of diagnosis. 1 No effective treatment for IPF existed until the approval of 2 antifibrotic drugs (pirfenidone and nintedanib) more than 10 years ago. These drugs were approved by the US Food and Drug Administration based on demonstration of significant drug-associated differences in slowing the decline in lung function in 2 randomized clinical trials 2 , 3 ; lung function was measured by forced vital capacity (FVC), which remains the main clinically relevant outcome for IPF.

Read More About

Zamora AC , Ortega VE , Carmona EM. When the Third Time Is Not the Charm—Trial Outcomes in Idiopathic Pulmonary Fibrosis. JAMA. 2024;332(5):374–376. doi:10.1001/jama.2024.8776

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What is turmeric good for? The spice has powerful antioxidants and other benefits

More than just adding flavor, color and aroma to our food, spices tell a story. Take turmeric, for example, which was first used nearly 4,000 years ago in India before spreading through China, East and West Africa and Jamaica. Turmeric also has a long history of religious significance and medicinal use in South Asia.

"Turmeric's main active component, curcumin , makes it a potential treatment for numerous health conditions," says Dr. Denise Millstine, a women's health and integrative medicine specialist at Mayo Clinic in Arizona.

Still, experts contend turmeric needs to be researched further to confirm the impact of these health benefits. 

What is turmeric?

A member of the ginger family, turmeric, also known as Curcuma longa, is a flowering plant whose rhizomes (roots) appear similar to the rhizomes of ginger − but with a yellowish-orange color instead of brown. Grated, sliced and  peeled  in its raw form or dried and ground into a powder, turmeric is used extensively in Indian cuisine especially, giving foods both flavor and color. The spice is commonly added to soups, tandoori chicken,  rice  and curry, and has become a popular enhancement in roasted vegetables and  egg scrambles .

Turmeric has also been used as a traditional Indian medicine for centuries and is widely available today as a supplement in the form of both powder and capsules. 

What is turmeric good for?

Though the  National Center for Complementary and Integrative Health  notes the health effects of turmeric supplementation on certain medical conditions "remain uncertain," turmeric does have properties known to be beneficial. For instance, as with other colorful plant-based foods, turmeric is rich in phytonutrients ( powerful antioxidants ), known to protect the body from  free radicals  like sunlight or air pollution and shield cells from damage.

"Turmeric  may also aid digestion , improve brain function, and support healthy skin," explains Lisa Young, PhD, an adjunct professor of nutrition at New York University and the author of "Finally Full, Finally Slim."

The active component, curcumin, is also known to "decrease and relieve some symptoms of mild arthritis , such as joint pain and joint inflammation," says Jessica Sepel, BHlth, a clinical nutritionist and founder of  JSHealth . Turmeric may also improve heart health by reducing bad cholesterol while increasing good cholesterol , Young says.

Curcumin may also have cancer-fighting properties, though such research is ongoing.

"Some studies suggest that curcumin may have anticancer properties by inhibiting the growth of cancer cells and preventing the formation of new blood vessels in tumors," says Jen Messer, a nutrition consultant and registered dietitian at  Jen Messer Nutrition .

How much turmeric to take daily?

Turmeric does have some known negative side effects. 

"While turmeric is safe to consume, too much of it can cause diarrhea, nausea and headache," Young says. Eating turmeric may also slow down blood clotting due to its anticoagulant properties, "which can be beneficial for some but dangerous to others," Young adds. 

Millstine notes that though she agrees that "turmeric is generally safe," there are other potential side effects to be mindful of. "The biggest risk I encounter with turmeric in my practice is interactions with other medications," she explains. Some forms of the plant may also cause heartburn .

While there is no standard established dose of turmeric to take daily, "The World Health Organization has determined an acceptable daily intake of turmeric powder as 1.4 milligrams per pound of body weight when turmeric powder is used as a spice in cooking," explains Messer. She adds that most research indicates turmeric's supplement form should be kept between 500 and 2,000 milligrams daily, "but an effective dose may vary on the condition being treated." 

"As with all herbal dietary supplements, there can be risks associated with consumption," Sepel says. "Therefore, I always recommend checking in with your health professional to ensure that it suits your individual needs." 

Discover more health tips for your daily diet: 

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Contributing: Clare Mulroy

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